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THE LIBRARY 
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THE UNIVERSITY 


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PRESENTED BY 


PROF. CHARLES A. KOFOID AND 


MRS. PRUDENCE W. KOFOID 








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Fn * PHYSIOLOGICAL AND PATHOLOGICAL: 
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MONTHS OF PEDRUARY, MARCH AND APRIL, 1858, 


pee “RUDOLF VIRCHOW, 


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‘PUBLIC PROFESSOR IN ORDINARY or PATHOLOGICAL ANATOMY, GENERAL PATHOLOGY, AND THERAPEUTICS, IN 
\ 


THE, UNIVERSITY OF BERLIN 5 DIRECTOR OF THE PATHOLOGICAL INSTITUTE, AND PHYSICIAN 
f : ‘ ‘ TO THE CHARITS oe Sa ETC, ETC, 
| 


TRANSLATED FROM THE SECOND EDITION OF THE ORIGINAL, 


BY 


FRANK CHANCE, B.A., M.B., Canras. 


LICENTIATE OF THE ROYAL COLLEGE OF PHYSICIANS, PHYSICIAN TO THE BLENHEIM FREE ie Fav He 
AND INFIRMARY, ; 


" 5 ¢” me 


WITH 
NOTES AND NUMEROUS EMENDATIONS, 


PRINOIPALLY FROM MS. NOTES OF THE AUTHOR, — 


AND 


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Iilustrated by 144 Engravings on Wood, 





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1863. 








JOHN GOODSIR, F.RS,, Ere, — 
aie PROFESSOR OF ANATOMY IN THE UNIVERSITY OF EDINBURGH, 
: AS ONE OF THE EARLIEST AND MOST: ACUTE OBSERY 


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| BOTH PHYSIOLOGICAL AND PATHOLOGICAL, _ 


i Sar 


THIS WORK ON 


CELLULAR PATHOLOGY 


i Pian. 


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AS A SLIGHT TESTIMONY OF HIS DEEP RESPECT — 


_ AND SINCERE ADMIRATION, - 


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AUTHOR’S PREFACE. 


Fd 


—_-9-e—_—_ 


. Tux lectures which I herewith lay before the medical public at 
large were delivered in the early part.of this year, in the new Pa- 
thological Institute of the University of Berlin, in the presence of 
a somewhat numerous assembly of medical men, for the most part 
physicians practising in the town. The object chiefly aimed at in 
them, illustrated as they were by as extensive a series of microscop~ 
ical preparations as it was in my power to supply, was to furnish a 
clear and connected explanation of those facts upon which, accord- 
ing to my ideas, the theory of life must now be based, and out of 
which also the science of pathology has now to be constructed, 
They were more particularly intended as an attempt to offer in a 
better arranged form than had hitherto been done, a view of the 
cellular nature of all vital processes, both physiological and patho- 
logical, animal and vegetable, so as distinctly to set forth what even 
the people have long been dimly conscious of, namely, the unity of 
life* in all organized beings, in opposition to the one-sided humoral 
and neuristical (solidistic) tendencies which have been transmitted 
from the mythical days of antiquity to our own times, and at the 
same time to contrast with the equally one-sided interpretations of a 
grossly mechanical and chemical bias—the more delicate mechanism 
and chemistry of the cell. 

In consequence of the great advances that have been made in the 
details of science, it has been becoming continually more and more 


* See Lect. I, p. 40 and Lect. XIV., pp. $22-324.—Trans, 


vi AUTHOR’S PREFACE. 


difficult to the majority of those who are engaged in practice, to 
obtain in the subjects treated on in these lectures that amount of 
personal experience which alone can guarantee a certain degree of 
accuracy of judgment. Day by day do those who are obliged to 
consume their best energies in the frequently so toilsome and so ex- 
hausting routine of practice find it becoming less and less possible for 
them, not only to closely examine, but even to understand the more 
recent medical works, For even the language of medicine is gra- 
dually assuming another appearance; well-known processes to which 
the prevailing system had assigned a certain place and name in the 
circle of our thoughts, change with the dissolution of the system 
their position and their denomination. When a certain action is 
transferred from the nerves, blood, or vessels to the tissues, when a 
passive process is recognized to be an active one, an exudation to be 
a proliferation, then it becomes absolutely necessary to choose other 
expressions whereby these actions, processes, and products shall be 
designated ; and in proportion as our knowledge of the more deli- 
cate modes, in which the processes of life are carried on, becomes 
more perfect, just in that proportion must the new denominations also 
be adapted to this more delicate ground-work of our knowledge. 

It would not be easy for any one to attempt to carry out the 
necessary reform in medical opinion with more respect for tradition 
than I have made it my endeavour to observe. Still my own expe- 
rience has taught me that even in this there is a certain limit. Too 
great respect is a real fault, for it favours confusion; a well-selected 
expression renders at once accessible to the understanding of all, 
what, without it, efforts prolonged for years would be able to render 
intelligible at most only toafew. As examples I will cite the terms, 
parenchymatous inflammation, thrombosis and embolia, leukemia | 
and ichorrhemia, osteoid and mucous tissue, cheesy and amyloid 
metamorphosis, and substitution of tissues. New names cannot be 
avoided, where actual additions to experimental (empirical) know- 
ledge are being treated of. 

On the other hand, I have already often been reproached with 
endeavouring to rehabilitate antiquated views in modern science. 
In respect to this I can, I think, say with a safe conscience that I am 
just as little inclined to restore Galen and Paracelsus to the position 


AUTHOR’S PREFACE. vii 


they formerly held, as I am afraid openly to acknowledge whatever 
truth there is in their views and observations, In fact, I find not 
only that the physicians of antiquity and the middle ages had not 
in all cases their senses shackled by traditional prejudices, but more 
than this, that among the people common sense has clung to certain 
truths, notwithstanding the criticism of the learned had pronounced 
them overthrown. What should hinder me from avowing that the 
criticism of the learned has not always proved correct, that system 
has not always been nature, and that a false interpretation does not 
impair the correctness of the fact? Why should I not retain good 
expressions, or restore them, even though false ideas have been 
attached to them? My experience constrains me to regard the term 
fluxion (active congestion— W allung)* as preferable to that of con- 
géstion; I cannot help allowing inflammation to be a definite form 
in which pathological processes display themselves, although I am 
unable to admit its claims to be regarded as an entity; and I must 
needs, in spite of the decided counter-statements of many investi- 
gators, maintain tubercle to be a miliary granule, and epithelioma a 
heteroplastic, malignant new-formation (cancroid), | 
Perhaps it is now-a-days a merit to recognise historic rights, for it 
is indeed astonishing with what levity those very men, who herald 
forth every trifle, which they have stumbled upon, as a discovery, 
pass their judgment upon their predecessors, I uphold my own 
rights, and therefore I also recognize the rights of others. This is 
the principle I act upon in life, in politics and in science. We owe 
it to ourselves to defend our rights, for it is the only guarantee for 
our individual development, and for our influence upon the commu- 
nity at large. Such a defence is no act of vain ambition, and it 
involves no renunciation of purely scientific aims. For, if we would 
serve science, we must extend her limits, not only as far as our own 
knowledge is concerned, but in the estimation of others, Now this 
estimation depends in a great measure upon the acknowledgment 
accorded to our rights, upon the confidence placed in our investiga- 
tions, by others; and this is the reason why I uphold my rights. 
In a science so directly practical as that of medicine, and at a time 


* See the Author’s ‘Handbuch der speciellen Path. und Therapie,’ Vol. I. p. 141. 


Vill AUTHOR’S PREFACE. 


when such a rapid accumulation of facts is taking place, as there is 
in ours, we are doubly bound to render our knowledge accessible to 
the whole body of our professional brethren. We would have 
reform, and not revolution: we would preserve the old, and add the 
new. But our contemporaries have a confused idea of the results 
of our activity. For only too much it is apt to appear as though 
nought but a confused and motley mass of old and new would 
thereby be obtained; and the necessity of combatting rather the 
false or exclusive doctrines of the more modern, than those of the 
older writers, produces the impression that our endeavours savour 
more of revolution than reformation. It is, no doubt, much more 
agreeable to confine oneself to the investigation and simple publica- 
tion of what one discovers, and to leave to others to “ take it to 
market” (verwerthen—exploiter), but experience teaches us that 
this is extremely dangerous, and in the end only turns out to the 
advantage of those who have the least tenderness of conscience. 
Let us undertake, therefore, every one of us to fulfil the duties both 
of an observer and of an instructor. 

The lectures, which I here publish with the view of accomplishing 
this double purpose, have found such very patient auditors, that 
they may perhaps venture to hope for indulgent readers likewise. 
How greatly they stand in need of indulgence, I myself feel very 
strongly. Every kind of lecture can only satisfy the actual hearers ; 
and especially when it is chiefly intended to serve as an explanation 
of drawings on a board, and microscopical preparations, it must 
necessarily appear heterogeneous and defective to the reader. When 
the intention is to give a concise view of a comprehensive subject, 
it necessarily becomes impossible to bring forward all the arguments 
that could be advanced, and to support them by the requisite quo- 
tations. In lectures such as these too the personal views of the lec- 
turer may seem to be brought forward with undue exclusiveness, but 
as it is his business to give a clear exposition of the actual state of 
the science of which he treats, he is obliged to define with precision 
the principles, the correctness of which he has proved by his own 
experience. 

I trust therefore that what I offer may not be taken for more than 
it is intended to be. Those, who have found leisure enough to keep 


AUTHOR'S PREFACE. Ix 


up their knowledge by reading the current medical literature, will 
find but little that is new in these lectures. The rest will not, by 
reading them, be spared the trouble of being obliged to study the 
subjects, which are here only briefly touched upon, more closely in 
_ the histological, physiological and pathological works. But they 
will at least be in possession of a summary of the discoveries which 
are the most important as far as the cellular theory is concerned, and 
they will easily be able to add their more accurate study of the in 
dividual subjects to the connected exposition which I here give them 
of the whole. Nay, this very exposition may perhaps afford a direct 
stimulus for such more accurate study; and if it do but this, it will 
have done enough. 

The time at my disposal was not sufficient to enable me to write 
out and revise a work like this. I was therefore constrained to have 
the lectures taken down in short-hand, just as they were delivered, 
and to publish them with but slight alterations. Herr Langenhaun 

has executed his stenographical task with great care. As far as the 
_ shortness of the time permitted, and wherever the text would other- 
wise have been difficult of apprehension to the inexperienced, I have 
had woodcuts made from the drawings on the board, and more par- 
ticularly from the microscopical preparations which were sent round. 
Completeness in this respect could not be attained, seeing that, even 
as it is, the publication of the work has been delayed some months 
int consequence of the preparation of the woodcuts. 


RUD. VIRCHOW. 


Misproy, August 20th, 1858. 


Pot Pi ee Ss 


AUTHOR’S PREFACE 


TO THE 


SECOND EDITION. 





THE present attempt to bring the results of my experience, which 


are at variance with what is ordinarily taught, before the notice of 


the medical public at large, in a connected form, has produced unex- 
pected results; it has found many friends and vigorous opponents. 
Both of these results are certainly very desirable; for my friends 
will find in this book no arbitrary settlement of questions, nothing 
systematical or dogmatical, and my opponents will be compelled at 
length to abandon their fine phrases and to set to work and examine 
the matters for themselves. Both can only contribute to the impul- 
sion and advancement of medical science. 

But still both have also their depressing point of view. When 
one has laboured for ten years with all the energy and zeal of which 
he was capable, and has laid the results of his investigations before 
the judgment of his contemporaries, one is only too apt to imagine 
that a considerable part, that perhaps the greater and more import- 
ant portion of them, would be pretty generally known, This was, 
as I have learned by experience, not the case with my labours. One 
of my critics attributes it to my bringing forward too many argu- 
ments and lengthy cases in support of my views. It may be so, but 
then I might perhaps have been allowed to expect that other critics 


would have sought for the proofs, which they did not find bere in 
xi 


Xl AUTHOR’S PREFACE TO THE SECOND EDITION. 


sufficient abundance, in the original works. For I had in the preface 
to the first edition expressly pointed out that those who had kept up 
their knowledge, by reading the current medical literature, would 
here find but little that was new to them. 

In this new edition I have contented myself with improving the 
language, with expressing in more precise terms what was liable to 
be misunderstood, and with expunging repetitions. There no doubt, 
still even now, remains a great deal requiring correction; but it 
seemed to me that the whole ought as far as possible to preserve the 
fresher impress of oral discourse, and of the unshackled range of 
thought which there prevails, if it were for the future still to serve 
as an active ferment to the labourers in the so very various fields 
of medical science and practice. For the book will have fulfilled its 
object, if it assists in the propagation, not of cellular pathology, but 
in general only of independent thought and investigation. 


RUD. VIRCHOW., 


BERLIN, June 7th, 1859. 


TRANSLATOR’S PREFACE. 


Proressor Vircuow and his works are so well known wherever 
the science of medicine is studied, that I think it quite unnecessary, 
to give any account of them here. 

When I arrived in Berlin in March, 1858, these lectures were in 
the course of delivery, and I was present at a few of the concluding 
ones, Subsequently, whilst attending the lectures, classes, and post- 
mortem examinations* which are held in the Pathological Institute 
by Professor Virchow, I had ample opportunities for seeing practical 
illustrations of most of the doctrines advocated in this book. It 
was natural, therefore, that I should feel a desire to translate these 
lectures, the more especially as I had every reason to suppose that 
the views put forward in them still remained unknown—in cop- 
sequence, no doubt, of their German dress—to a large proportion 
of the English medical public, although they had already, many of 
them several years previously, appeared in Professor Virchow’s 
larger works. 

The translation will in many instances be found to differ somewhat 
from the original, for numerous additions, subtractions, and substi- 
tutions have been made, many of them at the suggestion of the 
Author, many at my own, but all with the Author’s sanction. 

A few notes will be found, especially in the later lectures. Of 
these some are literal, some free translations of, or are based upon, 
answers I received from Professor Virchow to questions I had put 
to him, whilst others (pp. 352, 406, 415-416) were made entirely at 


* From 700 to 800 bodies are examined annually in the Institute. 
xiii 


XIV TRANSLATOR’S PREFACE. 


his own suggestion, and are literal translations of his words. In all 
cases, however, the notes have been submitted to the Author, and 
approved by him. 

An index too, I thought might be of service, and I have therefore 
added a tolerably full one. 

I cannot sufficiently thank Professor Virchow for the very great 
trouble—a trouble of which nobody but myself can have any idea— 
which he has taken in revising this translation, nor for the exceeding 
courtesy and kindness with which he has replied to the very numer- 
ous questions—many of them put for my own private information— 
which I have plagued him with. He has written me fully fifty let- 
ters, most of them very long ones; and when I reflect that he daily 
passes eight or nine hours at the Charité, that he reads all the more 
important German, French, and English medical works which appear, 

and is besides constantly engaged in publishing something fresh, I 
can scarcely conceive how he has managed to find time to write 
these letters, of which a large proportion reached me by return of 
post. | 

To Dr. Harris I must return my best thanks for the assistance he 
has rendered me in reading the proof-sheets, and correcting any 
errors of language into which I might have fallen, and also for 
kindly permitting me to consult him whenever I met with any diffi- 
culty—a permission of which I have availed myself most freely. 

The engravings will, I think, be found to be pretty faithful copies 
of the original woodcuts. 


51 WIMPOLE STREET, August 10th, 1860. 


a 


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11. 


T2. 


138. 
14. 
15. 


16. 


17. 


18. 


LIST OF WOOD-ENGRAVINGS. 


Vegetable cells from a young shoot of Solanum tuberosum . . ., 


. Cartilage-cells from the margin of ossification of growing cartilage. 
. Different kinds of cells and cell-formations. «. Hepatic cell. 6. Con- 


nective-tissue corpuscle. . Capillary vessel. d. Stellate cell froma 
lymphatic gland. e. Nerve-cell from the cerebellum . é : . 


. Formation of vegetable cells, according to Schleiden : ’ . 
. Pigment-cell (from the eye), smooth muscular fibre-cell (from the intes- 


tines), portion of a nerve-fibre with a double contour . 
Cartilage from the epiphysis of the humerus of a child 


. Cortical layer of a tuber of Solanum tuberosum . . ¢ 
. Longitudinal section of a young shoot of Syringa .  . 3 
. Pathological proliferation of cartilage from a costal cartilage . 


10. 


Young ova from the ovary of a frog ei) wet oe 


Cells from catarrhal ae ie and mucus-corpuscles, and a caperng 
cell) : ° ° ° ° ‘ ° ; 
Diagram of the ‘Asbulas ehisoi Paetss cme Ae aabcke Wye 


Diagram of the investment-(cluster-) theory .  . 


Cylindrical epithelium from the gall-bladder 

Transitional epithelium from the urinary bladder. ‘ : 

Perpendicular section through the surface of the skin of a toe (oidermi 
rete Malpighii, papillz) . . ; ‘ : : 

Diagrammatic representation of a ss em section oe a nail i in seta 
and pathological conditions . : . . . 

A. Development of sweat-glands. JB. Portion of the duct of a sweat- 
ee on ee 


PAGE 


32 


65 


68 


xvi 


FIG, 


19. 


20. 


21. 
22. 
23. 
24. 


25. 
26. 


27. 


28. 


29. 


30. 


31. 
32. 


33. 
34. 


35. 
36. 


37. 
38. 


39. 
40. 


41. 
42, 
48. 
44, 
45, 
46. 
4. 


48. 


49, 


BIST OF ENGRAVINGS. 


PAGE 
A. Bundle of ordinary connective tissue. B. Development of connective 
tissue according to Schwann’s plan, C. Development of connective 


tissue according to Henle’s plan. : : ; : : : po) 
Young connective tissue from the embryo of a pig . : ‘ ° 1 he 
Diagram of the development of connective tissue . . . : 18 
Section through the growing cartilage of a patella . : ° ‘ a7 a 
Primitive muscular fasciculi in different conditions . : ‘ : - “9 
Muscular elements from the heart of a puerperal woman . d 5 re 
Smooth muscular fibres from the urinary bladder . F ; ; . 838 
Small artery from the base of the cerebrum . ° : ‘ : . 86 
Diagrammatic representations of hepatic cells. .A. Physiological appear- 
ance. 8. Hypertrophy. C. Hyperplasy ; ; : ‘ : . 94 
Portion of the periphery of the liver of a rabbit, with the vessels in- 
jected. : : : : : . ‘ ° : : ‘ - 102 
Natural injection of the corpus striatum of a lunatic . : : . 104 
Injected preparation from the muscular coat of the stomach . : - 105 
Vessels in the cartilage of the caleaneum of a new-born child. : s 10F 
Bone. Longitudinal section from a cortex of a sclerotic tibia ; . 108 
Bone. Transverse section ; : : : ° : : ‘ 409 
Bone-corpuscles from a morbid formation of bone in the dura mater of 
the brain : ‘ : ‘ , ‘ , ‘ ; é foe et) 
Section of an osseous plate from the arachnoid of the brain . ‘ pba 
Longitudinal and transverse section from the semilunar cartilage of the 
knee-joint of a child ; : : Meas : : : ‘ mae is 
Transverse section from the tendo Achillis of an adult . : ; . 120 
Transverse section from the interior of the tendo Achillis of a new-born 
child . . . . . . . . ° . . +. 122 
Longitudinal section from the interior of the tendo Achillis of a new- 
born child. , . : . ; : 3 ; ; - 123 
The abdominal end of the umbilical cord of a nearly full-grown foie 
injected . . . : : : : : : : : : - 126 
Transverse section through a part of the umbilical cord . : : . 128 
Transverse section of the mucous tissue of the umbilical cord. : Pe ib 


Elastic networks and fibres from the subcutaneous tissue of the abdomen 132 


Injection of the vessels of the skin; vertical section é é ; . 186 
Section of the dartos ; ‘ ; : : ; - : eek od 
Small artery from the tendinous sheath of an extensor muscle. . . 142 


A. Epithelium from the femoral eas B. ea from veins of 


- considerable size . : . 145 


Epithelium from the vessels of the sidney. A, Fiat, sonal anata cells 
from a new-born child. 2B. Ribbon-like plate of epithelium from an adult 145 


Irregular contraction of small vessels from the web of a frog’s foot after 
the application of stimuli. Copied from Wharton Jones : : . 149 


LIST OF ENGRAVINGS. XVii 
FIG. 
50. Coagulated fibrine from human blood . : Tipe) ts Seer ‘168 
51. Nucleated blood-corpuscles from a human foetus, six otk old : - 170 
52. Blood-corpuscles from an adult 9 : : q - 171 
53. Crystals of Hematoidine . ; j SEES, ¥ ‘ ‘ ‘ - 175 
54. Pigment from an apoplectic cicatrix in the brain. : ° . 176 
55. Crystals of Hemine from human blood ‘ : : . 177 
56. Colourless blood-corpuscles ‘ é ‘ : ‘ ‘ é a . 180 
57. Colourless blood-corpuscles in variolous leucocytosis ‘ . 182 


58. Fibrine clot from the pulmonary artery, and a portion of a granule com- 
posed of thickly crowded colourless blood-corpuscles, in leucocytosis . 184 


59. Capillary stream in the web of a frog’s foot . ‘ ‘ 185 
60. Diagram of a bleeding-glass, with coagulated hyperinotic blood " - 187 
61. Sections through the cortical substance of human mesenteric glands . 208 


62. Lymph-corpuscles from the interior of the follicles of a oe 


gland. : ‘ FE isliake “ ; 2 : - 909 
63. Pus-corpuscles and their nuclei in Gonorrhea . : : 3 2 . 213 
64. Inspissated, cheesy pus. ; : : : : ; ; ; _ 214 
65. Inspissated, hemorrhagic pus, some of it in process of disintegration, 

from a case of Empyema : ; i ; 3 : : oe 


66. Pus engaged in fatty metamorphosis ; . "eehe Diliby rt . 216 
67. Section through the cortex of an axillary gland from an arm, the skin of 
which had been tattooed ‘ ‘ r é : : ‘ : . 219 
68. Reticulum of an axillary gland, filled with cinnabar, from an arm which 
had been tattooed . é 5 oa) eg : ¢ F : . 220 
69. Valvular thrombosis of the saphenous vein . é : é g . 282 
40, Puriform mass of débris from softened thrombi. .A. Granules seen in 
disintegrating fibrine. B. Colourless blood-corpuscles set free by 
the softening; some of them engaged in retrograde metamorphosis. 
@.. Red blood-corpuscles undergoing decolorization and disorganization 283 
41, Autochthonous and prolonged thrombi from branches of the femoral 


veins . oaiy : . . : ° : ; ‘eels . 289 
42. Embolia of the pulmonary artery . é ° ‘ ‘ . e . 241 
48. Ulcerative endocarditis affecting the mitral valve, from a puerperal wo- 

man . . : . : . : : : . 242 
74—T5. Capillary embolia in the tufts (en of the splenic artery after 

endocarditis . : . Or wes . 248 


46. Melanemia. Blood from the night aes, A Sa ee Se eee . 257 
44, Transverse section through one of the trunks of the brachial plexus . 266 
48. Grey and white nerve-fibres .  . ° ‘ ° . it cg ip a 
49. Medullary hypertrophy of the optic nerve within the eye. ° P . 268 
80. Drops of medullary matter. A. From the medullary sheath of cerebral 
nerves after they have become swollen up with water. 3B. Drops from 
disintegrating epithelium from the gall-bladder « +» + «+ «© 270 


2 


XVlil LIST OF ENGRAVINGS. 


FIG, 


81. 


82. 


88. 


84. 
85. 


86. 
87. 


88. 
89. 


90. 
rie 
92. 
93. 
94. 


95. 
96. 


97. 


98. 


99. 


100. 


101. 
102. 


103. 


104. 
105. 


106. 
107. 


108. 
109. 


PAGE 
Broad and narrow nerve-fibres with the medullary matter irregularly : 
swollenup . : : ‘ ‘ ; ; , ; , ‘ «212 
Vaterian or Pacinian body from the subcutaneous tissue of the end of 
a finger . ‘ : ; : ‘ : ; : i : : . 275 
Nervous and vascular papille from the skin of the end of a finger . . 277 
The fundamental substance of an acuminate ee of the es with 
abundant growth of papille . , : . 282 
A. Vertical section through the whole ae of the retina. B, C 
(after H. Muller). Isolated radiating fibres . ° ° : ‘ . 286 


Division of a primitive nerve-fibre . : : : ; ; ; . 289 

Nervous plexus from the submucous tissue of the intestinal canal of a 
child: «+5 : ‘ ‘ ; ‘ : ° , é ; : . 292 

Elements (ganglion-cells and nerve-fibres) from the Gasserian ganglion . 296 


Ganglion-cells from the great nervous centres. .A, B, (. From the spinal 
marrow. DD. From the cortex of the cerebrum . : A : . 298 
The half of a transverse section from the cervical part of the spinal 
marrow . : . : ‘ ; : ‘ : : . 804 
Diagrammatic representation of the Teen of the nerves in the cortex 
of the cerebellum, after Gerlach . : A : F : . 807 
Transverse section through the spinal marrow of Petromyzon duvistilis . 808 


Pale fibres from the spinal marrow of Petromyzon fluviatilis . : . 310 
Ependyma ventriculorum and neuro-glia. Ca. Corpora amylacea . . 813 
Cellular elements of the neuro-glia . ; : : ; : : . 316 
Diagrammatic representation of a transverse section of the spinal marrow 


in partial, grey atrophy . : ; 3 ; : ‘ . 319 
Diagram of the condition of the etennie of a nerve, a: when at rest, 

B, when in an electrotonic state—from Ludwig . ‘ ; 52028 
Convoluted tubule from the cortex of the kidney in morbus Bright . 835 


Parenchymatous keratitis . : : : ‘ ; . ‘ . . 341 
Perpendicular section of the cornea of the ox, from His. ‘ : . 842 
Horizontal section of the cornea, parallel to the surface, from His . . 843 
Parenchymatous keratitis . ; . . . x ‘ : . 844 
Division of nuclei in the cells of a melanotic tumour of ie parotid gland 346 
Cells from the marrow of bones, after Kolliker 3 ; ‘ ; . 847 
Division of nuclei in primitive muscular fasciculi from the immediate 
neighbourhood of a cancerous tumour . ; : é . . . 848 
Intra-capsular multiplication of cells in the central substance of an inter- 
vertebral cartilage . ‘ ° ° : ° . 849 
Adipose cellular tissue from the panniculus adiposus. | a Onde sub- 
cutaneous tissue, with fat-cells. 2B. Atrophic fat . : ‘ : . 862 


Interstitial growth of fat in muscle . : : : : ‘ ; . 864 

Intestinal villi, showing the absorption of fat. .A. Normal intestinal 
villus. 2B. Villus in a state of contraction. C@. Human intestinal villus 
during the absorption of chyle. D. Ina case of retention of chyle . 366 


LIST OF ENGRAVINGS, xix 


-_ 
110, The adjoining halves of two hepatic acini, showing the zones idouplie by rer 
fat, the amyloid matter and pigment —. . . org Biewret.. IR 
111. Hair-follicle with sebaceous glands from the skin ‘ é . 875 
112. Mammary gland during lactation, milk and colostrum, ° ‘ . 376 
118. Fatty degeneration of cerebral arteries. A. Fatty metamorphosis of 
the muscular cells of the circular-fibre coat. B. Formation of fat 
granule cells in the connective-tissue corpuscles of the internal coat . 881 
114, Fatty degeneration of the muscular substance of the heart in different 
stages . : . . : . ° : ° : ° ° - 384 
115. Corpora luteain the human ovary . . . . . , , = . 88% 
116. Vertical section through the walls of the aorta at a sclerotic part, in 
which an atheromatous dépét is already in the course of formation . 898 


117. The pultaceous atheromatous matter from a dépét in the aorta. aa’. Fluid 
fat. 6. Amorphous granularly-wrinkled flakes of tissue. , ¢’. Crystals 
of cholestearine . ° ; ; . : ‘ ‘ - 399 


118. Vertical section from a sclerotic plate i in the aorta (internal oat in pro- 
cess of fatty degeneration . . . ° , . : . 401 


119. Condylomatous excrescences of the miiteal valve , ‘ ¢ : - 405 
120. Laminated prostatic amyloid bodies (concretions) . ; ‘ é - 412 
121. Amyloid degeneration of a small ais from the submucous tissue of 

the small intestines : ° ‘ : ‘ : . 416 
122. Amyloid degeneration of a Nrnipheit lati a eT 8 - 425 
128. Corpora amylacea from a diseased lymphatic gland . eure - 0 426 
124, Proliferation of the growing cartilage of the diaphysis of the tibia of a 

child (longitudinal section) . . . : . . ‘ . 443 
125. Endogenous new formation; cells containing vesicles ‘ohimsfighoabay 

A. From the thymus gland of a new-born child. B, C. Cancer-cells . 444 
126. Vertical section through the romana. border of a growing i 

(pathological irritation) . j : ‘ ° . 455 
127—128. Horizontal sections through the growing i lla of the tibia, from 

a human foetus seven months old . : . ° ° : . . 459 


129. Line of demarcation in a piece of necrosed bone, from a case of pmwdar- 


throcace, bone-territories : . ‘ : - 462 
130. Periosteal growth of the cranial vhs tonite honk te achild) . . 468 
1381—132. Soft osteoma from the jaw of agoat .  . bb deve . 472, 474 


1383—134. Ricketty diaphysal cartilage, transformation into medullary and 
osteoid tissue; calcification and ossification . SON ‘ - 478,480 | 


135. Fracture of the humerus in process of healing; formation of callus  . 484 


136. Interstitial formation of pus in puerperal inflammation of muscle . . 490 
137. Purulent granulation from the subcutaneous tissue of a ae round 
about aligature .. wee om : ° ‘ . 496 


138. Development of cancer from connective tissue in carcinoma of the 
breast . A ° ‘ ° . . ‘ . ° . - « 499 


xx LIST OF ENGRAVINGS. 


: PAGn 
139. Commencing cauliflower growth (cancroid) of the neck of the uterus . 516 
140. Development of tubercle from connective tissue in the pleura . ; sib 
141. Mass of cancroid from a tumour of the under lip, with epidermic pearls . 528 
142. Canecer-cells . ‘ : . . : F : . ‘ ; . 529 
143. Cancroid of the orbit , 3 ; ° . ° . : : . 580 


144. Sarcoma of the breast ‘ 3 * ; : - rs ; p ea | 


CONTENTS. 


AvtHor’s PREFACE . Ff ; ; ‘ ‘ ‘ 
AvtHor’s Preracrk To THe Seconp Epirion . é ‘ 
TRANSLATOR’S PREFACE ; : ; A a : 
List or Woop Encravines é : ‘ i ‘ ‘ 


LECTURE I.—Cetzts anp tae CrtituLaAr Tueory . . 


Introduction and object. Importance of anatomical discoveries in the his- 
tory of medicine. Slight influence of the cell-theory upon pathology. 
Cells as.the ultimate active elements of the living body. Their nature 
more accurately defined. Vegetable cells; membrane, contents, nucleus. 
Animal cells; capsulated (cartilage) and simple. Nuclei of. Nucleoli of. 
Theory of the formation of cells out of free cytoblastema. Constancy 
of nucleus and its importance in the maintenance of the living cell. Di- 
versity of cell-contents and their importance as regards the functions of 
parts. Cells as vital unities. The body as a social organization. Cellu- 
lar in contradistinction to humoral and solidistic, pathology.—Explana- 
tion of some of the preparations. Young shoots of plants. Growth of 
plants. Growth of cartilage. Young ova. Young cells in sputa. 


LECTURE II.—Puaystotogicat Tissuzs . : : : 


Falsity of the view that tissues and fibres are made up of globules (ele- 
- mentary granules). The investment theory (Umhullungstheorie). Equi- 
vocal [spontaneous] generation of cells. The law of continuous deve- 
lopment.—General classification of the tissues. The three categories 
of General Histology. Special tissues. Organs and systems, or appara- 
tuses.—The Epiruettat Tissvzs. Squamous, cylindrical, and transitional 
epithelium. Epidermis and rete Malpighii. Nails, and their diseases, 
Crystalline lens. Pigment. Gland-cells.—The Connective Tissvgs. The 
theories of Schwann, Henle, and Reichert. My theory. Connective 
tissue as intercellular substance. Cartilage (hyaline, fibro- and reticular). 
Mucous tissue. Adipose tissue. Anastomosis of cells; juice-conveying 


system of tubes or canals. 
xxi 


51 


eet CONTENTS. 


; PAGE 
LECTURE III.—Puystotogican AND Parnotogioan Tissues 77 


The higher animal tissues: muscles, nerves, vessels, blood.—Muscles. Striped 
and smooth. Atrophy of. The contractile substance and contractility in 
general. Cutis anserina and arrectores pilorum. Vessels. Capillaries. 
Contractile vessels. Nerves.—Pathological tissues (Neoplasms), and their 
classification. Import of vascularity. Doctrine of specific elements. 
Physiological types (reproduction). Heterology (heterotopy, hetero- 
chrony, heterometry), and malignity. Hypertrophy and hyperplasy. 
Degeneration. Criteria for prognosis.—Law of continuity. Histological 
substitution and equivalents. Physiological and pathological substitution. 


LECTURE IV.—wNorrition anp trs CHANNELS F « 101 


Action of the vessels. Relations between vessels and tissues. Liver. Brain. 
Muscular coat of the stomach. Cartilage. Bone.—Dependence of tissues 
upon vessels. Metastases. Vascular territories [Gefissterritorien] (vas- 
cular unities). Conveyance of nutriment in the juice-conveying canals 
(Saftkandle) of the tissues. Bone. Teeth. Fibro-cartilage. Cornea. 
Semilunar cartilages. 


LECTURE V.—Nortrrrion, anp ConveYANcE oF THE Nv- 
TRITIVE JUICES . ‘ : : 3 ; : a td 


Tendons. Cornea. Umbilical cord.—Elastic tissue. Corium.—Loose con- 
nective tissue. Tunica dartos.—Importance of cells in the special dis- 
tribution of the nutritive juices. 


LECTURE VI.—Nortririon anp CrrcuLaTION . A . 140 


Arteries. Capillaries. Continuity of their membrane. Its porosity. Ha- 
morrhage by transudation (per diapedesin), Veins. Vessels during preg- 
nancy.— Properties of the walls of vessels: 1. Contractility. Rhythmical 
movement. Active or irritative hyperemia. Ischemia, Counter irritants, 
9. Elasticity and its importance as regards the rapidity and uniformity 
of the current of blood. Dilatation of the vessels. 3. Permeability. 
Diffusion. Specific affinities. Relations between the supply of blood 
and nutrition. Glandular secretion (liver). Specific action of the ele- 
ments of the tissues.—Dyscrasia, Its transitory character and local 
origin. Dyscrasia of drunkards. Hemorrhagic diathesis. Syphilis. 


LECTURE VII.—Tse Buoop . ; ; ; ‘ . 166 


Fibrine. Its fibrille. Compared with mucus, and connective tissue. Ho- 
mogeneous condition.—Red blood-corpuseles. Their nucleus and con- 
tents. Changes of form. Blood-crystals (Hamatoidine, Hemine, He- 
matocrystalline).—Colourless blood-corpuscles. Numerical proportion. 
Structure. Compared with pus-corpuscles. Their viscosity and aggluti- 
nation. Specific gravity. Crusta granulosa. Diagnosis between pus- 
and colourless blood-corpuscles. 


CONTENTS, Xxiii 


LECTURE VIII.—Bioop ann Lymph .  , ll, 189 

Change and replacement of the constituents of the blood. Fibrine. Lymph 
and its coagulation. Lymphatic exudation, Fibrinogenous substance, 
Formation of the buffy coat. Lymphatic blood, hyperinosis, phlogistic 
crasis. Local formation of fibrine. Transudation of fibrine. Forma- 
tion of fibrine in the blood. —Colourless blood-corpuscles (lymph-corpus- 
cles). Their increase in hyperinosis and hypinosis (Erysipelas, pseudo- 
erysipelas, typhoid fever). Leucocytosis and leukemia. Splenic and 
lymphatic leukemia.—The spleen and lymphatic glands as blood-making 
organs. Structure of lymphatic glands. 


LECTURE IX.—Pyzamia ann Levooortosis . ; _ ao 


Comparison between colourless blood- and pus-corpuscles, Physiological 
reabsorption of pus; incomplete (inspissation, cheesy transformation), 
and complete (fatty metamorphosis, or milky transformation). Intravasa- 
tion of pus.—Pus in the lymphatic vessels. Retention of matters in the 
lymphatic glands. Mechanical separation (filtration). Coloration by tat- 
tooing. Chemical separation (attraction): Cancer, Syphilis, Irritation of 
lymphatic glands, and its relation to leucocytosis.—Digestive and puer- 
peral (physiological) leucocytosis. Pathological leucocytosis (Scrofulosis, 
typhoid fever, cancer, erysipelas).—Lymphoid apparatuses: solitary and 
Peyerian follicles of the intestines. Tonsils and follicles of the tongue. 
Thymus. Spleen.—Complete rejection of pyemia as a dyscrasia suscep- 
tible of demonstration morphologically. 


LECTURE oe Menaveariaad, DysorAsit@ ; ‘ . 230 


Pyemia and phlebitis. Thrombosis. Puriform softening of thrombi. True 
and false phlebitis. Purulent cysts of the heart.—Embolia. Import of 
prolonged thrombi. Pulmonary metastases. Crumbling away of the 
emboli. Varying character of the metastases. Endocarditis and capil- 
lary embolia. Latent pyemia.—Infectant fluids. Diseases of the lym- 
phatic apparatuses and secreting organs. Chemical substances in the 
blood; salts of silver. Arthritis. Caleareous metastases. Diffuse me- 
tastatic processes. Ichorrhemia. Pyemia as a collective name.— 
Chemical dyscrasie. Malignant tumours, especially cancer. Diffusion 
by means of contagious parenchymatous juices. 


LECTURE XI.—Piementary Etements 1x tHE Buoop. 
NERVES : : ; : : : . ~ . 255 


Melanemia. Its relation to melanotic tumours and colorations of the 
spleen.—Red blood-corpuscles, Origin. Melanic forms. Chlorosis— 
Paralysis of the respiratory substance. Toxicwmia,—The nervous sys- 
tem. Its pretended unity.—Nerve-fibres. Peripheral nerves: their fas- 
ciculi, primitive fibres, and perineurium. Axis-cylinder (electrical sub- 
stance). Medullary substance (Myeline). Non-medullated and medul- 
lated fibres, Transition from the one kind to the other: hypertrophy 
of the optic nerve. Different breadth of the fibres. Their terminations, 
Pacinian and tactile bodies. 


XX1V CONTENTS. 


PAGE 


LECTURE XII.—Tusre Nervous System . : ; . 280 


Peripheral terminations of the nerves. Nerves of special sense. The skin 
and the distinction of vessel-, nerve-, and cell-territories in it. Olfactory 
mucous membrane. Retina. Division of nerve-fibres. The electrical 
organ of fishes. Muscles. Further consideration of nerve-territories.— 
Nervous plexuses with ganglioniform enlargements. Intestines.—Errors 
of the neuro-pathologists.—The great nervous centres. Grey substance. 
Ganglion- [nerve-] cells containing pigment. Varieties of ganglion- 
cells ; sympathetic cells in the spinal marrow and brain, motor and sensi- 
tive cells. Multipolar (polyclonous) ganglion-cells, Different nature of 
the processes of ganglion-cells. 


LECTURE XIII.—Spruvat Corp anp Brain . : . 802 


The spinal cord. White and grey matter. Central canal. Groups of gang- 
lion-cells. White columns and commissures.—The medulla oblongata 
and the brain. Its granular and bacillar layer—The spinal cord of the 
petromyzon and its non-medullated fibres.—The intermediate substance 
(interstitial tissue). Ependyma ventriculorum. Neuro-glia. Corpora 
amylacea. 


LECTURE XIV.—Acriviry anv Irrerrapititry or CELLv- 
LAR Exements. Dirrerent Forms or Irriration . 321 


Life of individual parts. The unity of the neurists. Consciousness, Activ- 
ity of individual parts. Excitability (irritability) as a general criterion of 
life. Meaning of irritation. Partial death. Necrosis.—Function, nutri- 
tion, and formation, as general forms of vital activity. Difference of 
irritability according to the different forms of activity.—Functional irri- 
tability. Nerves, muscles, ciliated epithelium, glands. Fatigue and fune- 
tional restitution. Stimuli. Their specific relations. Muscular irritabi- 
lity.—Nutritive irritability. Maintenance and destruction of elements. 
Inflammation. Cloudy swelling. Kidney (morbus Brightii) and cartilage. 
Neuro-pathological doctrines. Skin, cornea. The humoro-pathological 
doctrines. Parenchymatous exudation, and parenchymatous inflamma- 
tion.—Formative irritation. Multiplication of nucleoli and nuclei by 
division. Multi-nuclear cells; marrow-cells and myeloid tumours. Com- 
parison between formative muscular irritation and muscular growth. 
Multiplication (new formation) of cells by division. The humoro- and 
neuro-pathological doctrines.--Inflammatory irritation as a compound 
phenomenon. Neuro-paralytical inflammation (Vagus, Trigeminus). 


LECIURE XV.—Passtve Processes. Farry Dercenr- 
RATION. : P : : ; : ¢ ‘700 


Passive processes in their two chief tendencies to degeneration ; Necrobi- 
osis (softening and disintegration) and induration.—Fatty degeneration. 
Histological history of fat in the animal body; fat as a component of the 
tissues, as a transitory infiltration, and as a necrobiotic matter.—Adipose 
tissue. Polysarcia. Fatty tumours, Interstitial formation of fat. Fatty 





CONTENTS. xxv 


degeneration of muscles.—Fatty infiltration. Intestines ; structure and ee 


functions of the villi, Reabsorption and retention of the chyle. Liver; 
intermediate interchange of matter by means of the biliary ducts. Fatt 
liver.—Fatty metamorphosis, Glands; secretion of sebaceous matter ie 
milk (colostrum). Granule-cells and granule-globules. Inflammator 

globules. Arteries; fatty usure and atheroma in them. Fatty débris.. 


LECTURE XVI—A more Preciss Account or Farry 
MeraMoRPHOSIS . ? ; . , : ‘ . 883 


Fatty degeneration of muscles. Fatty metamorphosis of the substance of 
the heart. Formation of fat in the muscles in distortions.—Corpus lu- 
teum of the ovary. Fatty metamorphosis of pulmonary epithelium. 
Yellow softening of the brain. Arcus senilis.—Optical properties of 
fattily degenerated tissues. Renal epithelium in Bright’s disease. Succes- 
sive stages (cloudy swelling, fatty metamorphosis, fatty detritus (débris) 
atrophy). Inflammatory globules. Similarity of the result in Mr Pa, 
tory and non-inflammatory changes.—Atheromatous process in arteries, 
Its relation to ossification. Inflammatory character of the process; its 
analogy with endocarditis. Formation of the atheromatous deposit. Ap- 
pearance of cholestearine. Arterio-sclerosis. Endoarteritis, Calcifica- 
tion and ossification of arteries.—Mixed, activo-passive processes, 


LECTURE XVII.—Amynoiw Deceneration. InrtAmMa- 


TION . ‘ ; ; ‘ ‘ ; A ‘ . 409 

Amyloid (lardaceous or waxy) degeneration. Different nature of amyloid 
substances: concentric and laminated amyloid bodies (brain, prostate), 
and amyloid degeneration properly so called. Its course. Commence- 
ment of the affection in the minute arteries. Waxy liver. Cartilage. 
Dyscrasie (constitutional) character of the disease, Intestines. Kidneys: 
the three forms of Bright’s disease (amyloid degeneration, parenchyma- 
tous, and interstitial nephritis), Lymphatic glands. Functional disturb- 
ances of the affected organs.— Inflammation. The four cardinal symptoms 
and their predominance in the different schools: the thermic and vascu- 
lar theory ; the neuro-pathologists, exudations. Inflammatory stimuli, 
Lesion of function. Exudation as a consequence of the activity of the 
tissues; mucus and fibrine. - Inflammation as a complex irritative pro- 
cess. Parenchymatous and exudative (secretory) form. 


LECTURE XVIII.—Normat anp Parnotoaican New 


ForMATION .« ‘ ‘ é ; ‘ ' , . 438 
The theory of continuous development in opposition to the blastema and 
exudation theory—Connective tissue and its equivalents as the most 
general germ-store of new formations. Correspondence between embry- 
onic and pathological new formation. Cell-division as the most general 
starting-point of new-formations.—Endogenous formation. Physalides, 
Brood-cavities.—Different tendencies of new-formations. Hyperplasia, 
direct and indirect. Heteroplasia. Pathological formative cells. Differ- 
ence in their size and in the time required for their full development.— 
Description of the development of bone asa model-formation. Differ- 


XXV1 CONTENTS. 


PAGE 
ence between formation and transformation. Fresh and growing, in 


opposition to macerated, bone. Nature of medullary tissue—Growth in 
length of tubular [long] bones; proliferation of cartilage. Formation 
of marrow as a transformation of tissue; red and yellow, normal and 
inflammatory marrow. Osseous tissue, calcified cartilage, osteoid tissue. 
Bone-territories: caries, degenerative ostitis. Granulations in bone. 
Suppuration of bone. Maturation of pus. Ossification of marrow.— 
Growth of long bones in thickness: structure and proliferation of the 
periosteum.—Granulations as analogous to the medulla of bones, and as 
the starting-point of all heteroplastic development. 


LECTURE XIX.—ParnotocicaL, AND ESPECIALLY HeErtr- 
RroLogous, New Formation. : : ; . . 471 


Consideration of some forms of pathological formation of bone. Soft oste- 
oma of the maxille. Rickets. Formation of callus after fracture.— 
Theory of substitutive new formation in opposition to exudative. De- 
structive nature of new-formations. Homology and heterology (malig- 
nity). Ulceration. Mollities ossium. Proliferation and luxuriation. 
Medulla of bones, and pus.—Suppuration. Its two forms: superficial, 
occurring in epithelium ; and deep, in connective tissue. Eroding suppue 
ration (skin, mucous membrane): pus- and mucus-corpuscles in their 
relations to epithelium. Ulcerative suppuration. Solvent properties of 
pus.—Connection of destruction with pathological growth and prolifera- 
tion. Correspondence of the first stage in pus, cancer, sarcoma, etc. 
Possible duration of the life of pathologically new-formed elements, and of 
pathological new-formations considered as wholes (tumours). Compound 
nature of the larger tuberous tumours (Geschwulstknoten), and miliary 
character of the real foci (Heerde). Conditions of growth and recurrence: 
contagiousness of new-formations and import of the anastomoses of cells. 
Cellular pathology in opposition to the humoral and neuristic. General 
infection of the body. Parasitism and autonomy of new-formations. 


LECTURE XX.—Form anp Nature or PatHoLoaicaL 
NEW-FORMATIONS . : : : : : ; 2-007 


Nomenclature and classification of pathological new-formations. Consist- 
ence ag a principle of division, Comparison with individual parts of the 
body. Histological division. Apparent heterology of tubercle, colloid, etc. 
—Difference of form and nature: Colloid, Epithelioma, Papillary tumour, 
Tubercle.—Papillary tumours: simple (condylomata, papillomata) and 
specific (villous cancer and cauliflower-tumour).—Tubercle: infiltration 
and granulation. Inflammatory origin of tubercle. Its production from 
connective tissue. Miliary granules, and solitary masses. The cheesy 
metamorphosis.—Colloid: myxoma. Collonema. Mucous or gelatinous 
cancer.—Physiological types of heterologous new-formations: lymphoid 
nature of tubercle, heematoid of pus, epithelioid of cancer, cancroid, pearly 
and dermoid tumours, and connective-tissue-like of sarcoma. Infec- 
tiousness according to the amount of juice.—Comparison between pathoe 
logical new-formations in animals and vegetables. Conclusion. . 


Las Ketsidee Hat detest uet de 


FEBRUARY 10, 1858. 
CELLS AND THE CELLULAR THEORY. 


Introduction and object—Importance of anatomical discoveries in the history of 
medicine—Slight influence of the cell-theory upon pathology—Cells as the ulti- 
mate active elements of the living body—Their nature more accurately defined 
—Vegetable cells; membrane, contents, nucleus—Animal cells; capsulated 
(cartilage) and simple—Nuclei of—Nucleoli of—Theory of the formation of 
cells out of free cytoblastema—Constancy of nucleus and its importance in the 
maintenance of the living cell—Diversity of cell-contents and their importance 
as regards the functions of parts—Cells as vital unities—The body as a social. 
_organization—Cellular, in contradistinction to humoral and | solidistic, pathology. 

fesiplamasion of some of the preparations—Young shoots of plants—Growth of plants 
—Growth of cartilage—Young ova—Young cells in sputa. 


GENTLEMEN,— Whilst bidding you heartily weleome to 
benches which must have long since ceased to be familiar 
to you, I must begin by reminding you, that it is not my 
want of modesty which has summoned you hither, but 
that I have only yielded to the repeatedly manifested 
wishes of many among you. Nor should I have ventured 
either to offer you lectures after the same fashion in which 
I am accustomed to deliver them in my regular courses. 
On the contrary, I will make the attempt to lay before you 
in a more succinct manner the development which I my- 
self, and, I think, medical science also, have passed through 
in the course of the last fifteen years. In my announce- 


ment of these lectures, I described the subject of ipa in 


28 LECTURE I. 


such a way as to couple histology with pathology ; and 
for this reason, that I thought I must take it for granted 
that many busily occupied physicians were not quite 
familiar with the most recent histological changes, and did 
not enjoy sufficiently frequent opportunities of examining 
microscopical objects for themselves. Inasmuch as, how- 
ever, itis upon such examinations that the most import- 
ant conclusions are grounded which we now draw, you 
will pardon me if, disregarding those among you who 
have a perfect acquaintance with the subject, I behave 
just as if you all were not completely familiar with the 
requisite preliminary knowledge. 

The present reform in medicine, of which you have all 
been witnesses, essentially had its rise in new anatomical 
observations, and the exposition also, which I have to 
make to you, will therefore principally be based upon 
anatomical demonstrations. But for me it would not be 
sufficient to take, as has been the custom during the last 
ten years, pathological anatomy alone as the groundwork 
of my views ; we must add thereto those facts of general 
anatomy also, to which the actual state of medical science 


is due. The history of medicine teaches us, if we will - 


only take a somewhat comprehensive survey of it, that 
at all times permanent advances have been marked by 
anatomical innovations, and that every more important 
epoch has been directly ushered in by a series of import- 
ant discoveries concerning the structure of the body. So 
it was in those old times, when the observations of the 
Alexandrian school, based for the first time upon the 
anatomy of man, prepared the way for the system of 
Galen ; so it was, too, in the Middle Ages, when Vesa- 
lius laid the foundations of anatomy, and therewith be- 
gan the real reformation of medicine ; so, lastly, was it 
at the commencement of this century, nee Bichat deve- 
loped the principles of general anatomy. What Schwann, 


t 


IMPORT OF THE CELL-THEORY. 29 


however, has done for histology, has as yet been but in 
a very slight degree built up and developed for pathology, 
and it may be said that nothing has penetrated less 
deeply into the minds of all than the cell-theory in its 
intimate connection with pathology. 

If we consider the extraordinary influence which Bichat 
in his time exercised upon the state of medical opinion, 
it is indeed astonishing that such a relatively long period 
should have elapsed since Schwann made his great dis- 
coveries, without the real importance of the new facts 
having been duly appreciated. This has certainly been 
essentially due to the great incompleteness of our know- 
ledge with regard to the intimate structure of our tissues 
which has continued to exist until quite recently, and, as 
we are sorry to be obliged to confess, still even now 
_ prevails with regard to many points of histology to such 
a degree, that we scarcely know in favout of what view 
to decide. Bey dedh du 

Hspecial difficulty has been found in answering the 
question, from what parts of the body action really pro- 
-ceeds—what parts are active, what passive ; and yet itis 
already: quite possible to come to a definitive conclusion 
“upon this point, even in the case of parts the structure 
of which is still disputed. The chief point in this appli- 
cation of histology to pathology is to obtain a recognition 
of the fact, that the cell is really the ultimate morpholo- 
~ gical element in which there is any manifestation of life, 
and that we must not transfer the seat of real action to 
any point beyond the cell.. Before you, I shall have no 
particular reason to justify myself, if in this respect I 
make quite a special reservation in favour of life, In the 
course of these lectures you will be able to convince 
yourselves that it is almost impossible for any one to 
entertain more mechanical ideas in particular instances 

than I am wont to do, when called upon to interpret the 


30 LECTURE I. 


individual processes of life. But I think that we must 
look upon this as certain, that, however much of the 
more delicate interchange of matter, which takes place 
within a cell, may not concern the material structure 
as a whole, yet the real action does proceed from the 
structure as such, and that the living element only main- 
tains its activity as long as it really presents itself to us 
as an independent whole. 

In this question it is of primary importance (and you 
will excuse my dwelling a little upon this point, as it is 
one which is still a matter of dispute) that we should 
determine what is really to be understood by the term 
cell. Quite at the beginning of the latest phase of his- 
-tological development, great difficulties sprang up in 
crowds with regard to this matter. Schwann, as you no 
doubt recollect, following immediately in the footsteps 
of Schleiden, fnterpreted his observations according to 
botanical standards, so that all the doctrines of vegetable 
physiology were invoked, in a greater or less degree, to 
decide questions relating to the physiology of animal 
bodies. Vegetable cells, however, in the light in which 
they were at that time universally, and as they are even 
now also frequently regarded, are structures, whose 
identity with what we call animal cells cannot be ad- 
mitted without reserve. 

When we speak of ordinary vegetable cellular tissue, 
we generally understand thereby a tissue, which, in its 
most simple and regular form is, in a transverse section, 
seen to be composed of nothing but four- or six-sided, 
or, if somewhat looser in texture, of roundish or poly- 
gonal bodies, in which a tolerably thick, tough wall 
(membrane) is always to be distinguished. If now a 
single one of these bodies be isolated, a cavity is found, 
enclosed by this tough, angular, or round wall, in the 
interior of which very different substances, varying ac- 


VEGETABLE CELLS. 31 


cording to circumstances, may be deposited, e. g. fat, 
starch, pigment, albumen (ced/-contents). But also, quite 
independently of these local varieties in the contents, we 
are enabled, by means of chemical investigation, to 
detect the presence of several different substances in the 
essential constituents of the cells. 

The substance which forms the external membrane, 
and. is known under the name 
of cellulose, is generally found 
to be destitute of nitrogen, and 
yields, on the addition of iodine 
and sulphuric acid, a peculiar, 
very characteristic, beautiful 
blue tint. Iodine alone produces no colour ; sulphuric - 
acid by itself chars. The contents of simple cells, on the_‘ 





other hand, do not turn blue ; when the cell is quite a_. Wate 


simple one, there appears, on the contrary, after the addi- 
tion of iodine and sulphuric acid, a brownish or yellowish 
mass, isolated in the interior of the cell-cavity as a spe- 
cial body (protoplasma), around which can be recognised 
a special, plicated, frequently shrivelled membrane (pr7- 
mordial utricle) (fig. 1, c). Even rough chemical analysis 
generally detects in the simplest cells, in addition to 
the non-nitrogenized (external) substance, a nitrogenized 
internal mass ; and vegetable physiology seems, there- 
fore, to have been justified in concluding, that what really 
constitutes a cell is the presence within a non-nitro- 


Fig. 1. Vegetable cells from the centre of the young shoot of a tuber of 
Solanum tuberosum. a. The ordinary appearance of the regularly polygonal, 
thick-walled cellular tissue. 6. An isolated cell with finely granular-looking cavity, 
in which a nucleus with nucleolus is to be seen. c¢. The same cell after the addition 
of water; the contents (protoplasma) have receded from the wall (membrane, 
capsule). Investing them a peculiar, delicate membrane (primordial utricle) 
has become visible. d. The same cell after a more lengthened exposure to the 
action of water; the interior cell (protoplasma with the primordial utricle and 
nucleus) has become quite contracted, and remains attached to the cell-wall (cap- 
sule) merely by the means of fine, some of them branching, threads. 


32 LECTURE I. 


genized membrane of. nitrogenized contents differing 
from it. | 7 

It had indeed already long been known, that other 
things besides existed in the interior of cells, and it was 
one of the most fruitful of discoveries when Robert 
Brown detected the nucleus in the vegetable cell. But 
this body was considered to have a more important 
share in the formation than in the maintenance of cells, 
because in very many vegetable cells the nucleus be- 
comes extremely indistinct, and in many altogether dis- 
appears, whilst the form of the cell is preserved. 

These observations were then applied to the consider- 
ation of animal tissues, the correspondence of which 
with those of vegetables Schwann endeavoured to de- 
monstrate. The interpretation, which we have just 
mentioned as having been put upon the ordinary forms 
of vegetable cells, served as the starting-point. In this, 
however, as after-experience proved, an error was 
committed. Vegetable cells cannot, viewed in their 
entirety, be compared with all animal cells. In animal 
cells, we find no such distinctions between nitrogenized 
and non-nitrogenized layers; in all the essential con- 
stituents of the cells nitrogenized matters are met with. 
But there are undoubtedly certain forms in the animal 
body which immediately recall these forms of vegetable 
cells, and among them there are none so characteristic 
as the cells of cartilage, which is, in all its features, ex- 
tremely different from the other tissues of the animal 
body, and which, especially on account of its non-vascu- 
larity, occupies quite a peculiar position. Cartilage in 
every respect stands in the closest relation to vegetable 
tissue. In a well-developed cartilage-cell we can dis- 
tinguish a relatively thick external layer, within which, 
upon very close inspection, a delicate membrane, con- 
tents, and a nucleus are also to be found. Here, there- 


ANIMAL CELLS. _ 33 


fore, we have a structure which entirely corresponds 
with a vegetable cell. 

It has, however, been customary with authors, when 
describing cartilage, to call the whole of the structure 
of which I have just given you a sketch (fig. 2, a—d) 
a cartilage-corpuscle, and in consequence of this having 
been viewed as analogous to the cells in other parts of 
animals, difficulties have arisen 
by which the knowledge of the 
true state of the case has been 
exceedingly obscured. <A carti- 
lage-corpuscle, namely, is not, as => 
a whole, a cell, but the external 2 
layer, the capsule, is the product 
of a later development (secretion, excretion). In young 
cartilage it is very thin, whilst the cell also is generally 
smaller. If we trace the development still farther back, 
we find in cartilage, also, nothing but simple cells, iden- 
tical in structure with those which are seen in other 
animal tissues, and not yet possessing that external 
secreted layer. 

You see from this, gentlemen, that the comparison 
between animal and vegetable cells, which we certainly 
cannot avoid making, is in general inadmissible, because 
in most animal tissues no formed elements are found 
which can be considered as the full equivalents of vege- 
table cells in the old signification of the word ; and be- 
cause in particular, the cellulose membrane of vegetable 
cells does not correspond to the membrane of animal 
ones, and between this, as containing nitrogen, and the 
former, as destitute of it, no typical distinction is pre- 
sented. On the contrary, in both cases we meet with a 





Fig. 2. Cartilage-cells as they occur at the margin of ossification in growing 
cartilage, quite analogous to vegetable cells (cf. the explanation to fig. 1). a—¢. In 
a more advanced stage of development. d. Younger form. 

3 


34 LECTURE I. 


body essentially of a nitrogenous nature, and, on the 
whole, similarin composition. The so-called membrane 
of the vegetable cell is only met with in a few animal 
tissues, as, for example, in cartilage ; the ordinary mem- 
brane of the animal cell corresponds, as I showed as far 
back as 1847, to the primordial utricle of the vegetable 
cell. It is only when we adhere to this view of the 
matter, when we separate from the cell all that has been 
added to it by an after-development, that we obtain a 
simple, homogeneous, extremely monotonous structure, 
recurring with extraordinary constancy in living organ- 
isms. But just this very constancy forms the best crite- 
terion of our having before us in this structure one of 
those really elementary bodies, to be built up of which 
is eminently characteristic of every living thing—without 
the pre-existence of which no living forms arise, and to 
which the continuance and the maintenance of life is 
intimately attached. Only since our idea of a cell has 
assumed this severe form—and I am somewhat proud of 
having always, in spite of the reproach of pedantry, 
firmly adhered to it—only since that time can it be said 
that a simple form has been obtained which we can 
everywhere again expect to find, and which, though. 
different in size and external shape, is yet always 
* identical in its essential constituents. 

In such a simple cell we can distinguish dissimilar 
constituents, and it is important that we should accurately 
define their nature also. 

In the first place, we expect to find a nucleus within 
the cell; and with regard to this nucleus, which has 
usually a round or oval form, we know that, particularly 
in the case of young cells, it offers greater resistance to 
the action of chemical agents than do the external parts 
of the cell, and that, in spite of the greatest variations in 
the external form of the cell, it generally maintains its 


THEORY OF FREE CELL-FORMATION. 35 


form. The nucleus is accordingly, in cells of all shapes 
that part which is the most constantly found unchanged. 
There are indeed isolated cases, which lie scattered 
throughout the whole series of facts in comparative 
anatomy and pathology, in which the nucleus also has a 
stellate or angular appearance ; but these are extremely 
rare exceptions, and dependent upon peculiar changes 
which the element has undergone. Generally, it may be 
said that, as long as the life of the cell has not been 





brought to a close, as long as cells behave as elements 
still endowed with vital power, the nucleus maintains a 
very nearly constant form. 

The nucleus, in its turn, in completely developed cells, 
very constantly encloses another structure within itself 
—the so-called nucleolus. With regard to the question 
of vital form, it cannot be said of the nucleolus that it 
appears to be an absolute requisite ; and, in a considera- 
ble number of young cells, it has as yet escaped detec- 
tion. On the other hand, we regularly meet with it in 
fully developed, older forms ; and it, therefore, seems to 
mark a higher degree of development in the cell. Ac- 
cording to the view which was put forward in the first 
instance by Schleiden, and accepted by Schwann, the 


Fig.8. a. Hepatic cell. 6. Spindle-shaped cell from connective tissue, ¢. Oa- 
pillary vessel. d. Somewhat large stellate cell from a lymphatic gland. e¢. Ganglion- 
cell from the cerebellum, The nuclei in every instance similar. 


36 LECTURE I. 


connection between the three coexistent cell-constituents 
was long thought to be on this wise: that the nucleolus 
was the first to shew itself in the development of tissues, 
by separating out of a formative fluid (d/astema, cyto- 
blastema), that it quickly attained a certain size, that then 
fine granules were precipitated out of the blastema and 
settled around it, and that about these there condensed 
a membrane. That in this way a nucleus was completed, 
about which new matter gradually gathered, and in due 
time produced a little membrane (the celebrated watch- 
Fie. 4. glass form, fig. 4, d’). This descrip- 
tion of the first development of cells 
out of free blastema, according to 
which the nucleus was regarded as 
preceding the formation of the cell, 
, and playing the part of a real cell- 
former (cytoblast), is the one which is usually concisely 
designated by the name of the cell-theory (more accu- 
rately, theory of free cell-formation),—a theory of deve- 
lopment which has now been almost entirely abandoned, 
and in support of the correctness of which not one sin- 
gle fact can with certainty be adduced. With respect to 
the nucleolus, all that we can for the present regard as 
certain, is, that where we have to deal with large and 
fully developed cells, we almost constantly see a nucleo- 
lus in them ; but that, on the contrary, in the case of 
many young cells it is wanting. 
You will hereafter be made acquainted with a series 





c) 


Fig. 4. From Schleiden, ‘ Grundzuge der wiss. Botanik,’ I, fig. 1. ‘ Contents of 
the embryo-sac of Vicia faba soon after impregnation. In the clear fluid, con- 
sisting of gum and sugar, granules of protein-compounds are seen swimming about 
(a), among which a few larger ones are strikingly conspicuous. Around these lat- 
ter the former are seen conglomerated into the form of a small disc (0, ¢). Around 
other discs a clear, sharply defined border may be distinguished, which gradually 
recedes farther and farther from the dise (the cytoblast), and, finally, can be dis- 
tinctly recognised to be a young cell (d, e).” 


IMPORT OF THE NUCLEUS AND CELL-CONTENTS. 37 


of facts in the history of pathological and physiological 
development, which render it in a high degree probable ».. 
that the nucleus plays an extremely important part 
within the cell—a part, I will here at once remark, less 
connected with the function and specific office of the 
cell, than with its maintenance and multiplication as a 
living part. The specific (in a narrower sense, animal) 
function is most distinctly manifested in muscles, nerves, 
and gland-cells; the peculiar actions of which—con- 
traction, sensation, and secretion—appear to be con- 
nected in no direct manner with the nuclei. But that, 
whilst fulfillmg all its functions, the element remains 
an element, that it is not annihilated nor destroyed 
by its continual activity—this seems essentially to 
depend upon the action of the nucleus. All those 
cellular formations which lose their nucleus, have a 
more transitory existence; they perish, they disap- 
pear, they die away or break up. A human blood-cor- 
puscle, for example, is a cell without a nucleus ; it pos- 
sesses an external membrane and red contents; but 
herewith the tale of its constituents, so far as we can 
make them out, is told, and whatever has been recounted 
concerning a nucleus in blood-cells, has had its founda- 
tion in delusive appearances, which certainly very easily 
can be, and frequently are, occasioned by the production 
of little irregularities upon the surface (Fig. 52). We 
should not be able to say, therefore, that blood-corpuscles 
were cells, if we did not know that there is a certain 
period during which human blood-corpuscles also have 
nuclei; the period, namely, embraced by the first 
months of intra-uterine life. Then circulate also in the . 
human body nucleated blood-cells, like those which we 
see in frogs, birds, and fish throughout the whole of their 
lives. In mammalia, however, this is restricted to a cer- 
tain period of their development, so that at a later stage 


38 LECTURE I. 


the red blood-cells no longer exhibit all the characteris- 
tics of a cell, but have lost an important constituent in 
their composition. But we are also all agreed upon 
this point, that the blood is one of those changeable 
constituents of the body, whose cellular elements possess 
no durability, and with regard to which everybody 
assumes that they perish, and are replaced by new ones, 
which in their turn are doomed to annihilation, and 
everywhere (like the uppermost cells in the cuticle, in 
which we also can discover no nuclei, as soon as they 
begin to desquamate) have already reached a stage in 
their development, when they no longer require that 
durability in their more intimate composition for which 
we must regard the nucleus as the guarantee. 

On the other hand, notwithstanding the manifold inves- 
tigations to which the tissues are at present subjected, 
we are acquainted with no part which grows or multi- 
plies, either in a physiological or pathological manner, in 
which nucleated elements cannot invariably be demon- 
strated as the starting-points of the change, and in which 
the first decisive alterations which display themselves, do 
not involve the nucleus itself, so that we often can deter- 
mine from its condition what would possibly have become 
of the elements. 

You see from this description that, at least, two differ- 
ent things are of necessity required for the composition 
of a cellular element; the membrane, whether round, . 
jagged or stellate, and the nucleus, which from the out- 
set differs in chemical constitution from the mem- 
brane. Herewith, however, we are far from having 
enumerated all the essential constituents of the cell, 
for, in addition to the nucleus, it is filled with a rela- 
tively greater or less quantity of contents, as is like- 
wise commonly, it seems, the nucleus itself, the contents 
of which are also wont to differ from those of the 


IMPORT OF THE NUCLEUS AND CELL-CONTENTS. 89 


cell. Within the cell, for example, we see pigment, 
without the nucleus containing any. Within a smooth 
muscular fibre-cell, the contractile sub- 
stance is deposited, which appears to be 
the seat of the contractile force of mus- 
cle; the nucleus, however, remains a 
nucleus. The cell may develop itself into 
a nerve-fibre, but the nucleus remains, 
lying on the outside of the medullary 
[white'] substance, a constant constituent. 
Hence it follows, that the special peculiar- 
ities which individual cells exhibit in 
particular places, under particular circum- 
stances, are in general dependent upon the 
varying properties of the cell-contents, 
and that it is not the constituents which 
we have hitherto considered (membrane 
and nucleus), but the contents (or else the masses : 
of matter deposited without the cell, %ntercellular), 
which give rise to the functional (physiological) dif- 
ferences of tissues. For us it is essential to know 
that in the most various tissues these constituents, 
which, in some measure, represent the cell in its abstract 
form, the nucleus and membrane, recur with great con- 
stancy, and that by their combination a simple element 
is obtained, which, throughout the whole series of living 
vegetable and animal forms, however different they may 
be externally, however much their internal composition 
may be subjected to change, presents us with a structure 


Fia. 





Fig. 5. a. Pigment-cell from the choroid membrane of the eye. 5. Smooth mus- 
cular fibre-cell from the intestines, ec. Portion of a nerve-fibre with a double con- 
tour, axis-cylinder, medullary sheath and parietal, nucleolated nucleus. 


1 All words included in square brackets have been inserted by the Translator, and 
are intended to be explanatory. 


40 LECTURE I. 


of quite a peculiar conformation, as a definite basis for 
all the phenomena of life. 

According to my ideas, this is the only possible start- 
ing-point for all biological doctrines. If a definite cor- 
respondence in elementary form pervades the whole series 
of all living things, and if in this series something else 
which might be placed in the stead of the cell be in vain 
sought for, then must every more highly developed 
organism, whether vegetable or animal, necessarily, 
above all, be regarded as a progressive total, made up of 
larger or smaller number of similar or dissimilar cells. 
Just as a tree constitutes a mass arranged in a definite 
manner, in which, in every single part, in the leaves as 
in the root, in the trunk as in the blossom, cells are dis- 
covered to be the ultimate elements, so is it also with 
the forms of animal life. Every animal presents itself as 
a sum of vital unities, every one of which manifests all 
the characteristics of life. The characteristics and unity 
of life cannot be limited to any one particular spot in a 
highly developed organism (for example, to the brain of 
man), but are to be found only in the definite, constantly 
recurring structure, which every individual element dis- 
plays. Hence it follows that the structural composition 
of a body of considerable size, a so-called individual, 
always represents a kind of: social arrangement of parts, 
an arrangement of a social kind, in which a number of 
individual existences are mutually dependent, but in 
such a way, that every element has its own special 
action, and, even though it derive its stimulus to activity 
from other parts, yet alone effects the actual performance 
of its duties. 

I have therefore considered it necessary, and I believe 
you will derive benefit from the conception, to portion 
out the body into cell-territories (Zellenterritorien). I 
say territories, because we find in the organization of | 


CELL-TERRITORIES AND INTERCELLULAR SUBSTAN CE. 41 


animals a peculiarity which in vegetables is scarcely at 
all to be witnessed, namely, the development of large 
masses of so-called ¢ntercellular substance. Whilst vege- 
table cells are usually in immediate contact with one 
another by their external secreted layers, although in 
such a manner that the old boundaries can still always 


Fie 6. 





be distinguished, we find in animal tissues that this 
species of arrangement is the more rare one. In the 


often very abundant mass of matter which lies between 


the cells (entermediate, intercellular substance), we are 


seldom able to perceive at a glance, how far a given 


part of it belongs to one or another cell ; it presents the 
aspect of a homogeneous intermediate substance. 
According to Schwann, the intercellular substance was 
the cytoblastema, destined for the development of new 
cells. This I do not consider to be correct, but, on the 
contrary, I have, by means of a series of pathological 
observations, arrived at the conclusion that the intercel- 
lular substance is dependent in a certain definite manner 
upon the cells, and that it is necessary to draw bounda- 


Fig. 6. Cartilage from the epiphysis of the lower end of the humerus of a child. 
The object was treated first with chromate of potash, and then with aceticacid. In 
the homogeneous mass (intercellular substance) are seen, at a, cartilage-cavities 
(Knorpelhohlen) with walls still thin (capsules), from which the cartilage-cells, pro- 
vided with a nucleus and nucleolus, are separated by a distinct limiting membrane. 
b. Capsules (cavities) with two cells produced by the division of previously simple 
ones. ¢. Division of the capsules following the division of the cells. d. Separa- 


tion of the divided capsules by the deposition between them of intercellular sub- 


stance—Growth of cartilage. 


49, LECTURE I. 


ries in it also, so that certain districts belong to one cell, 
and certain others to another. Yow will see how sharply 
these boundaries are defined by pathological processes 
(Fig. 129), and how direct evidence is afforded, that any 
given district of intercellular substance is ruled over by 
the cell, which lies in the middle of it and exercises 
influence upon the neighbouring parts. 

It must now be evident to you, I think, what I under- 
stand by the territories of cells. But there are simple 
tissues which are composed entirely of cells, cell lying 
close to cell. In these there can be no difficulty with 
regard to the boundaries of the individual cells, yet it is 
necessary that I should call your attention to the fact 
that, in this case, too, every individual cell may run its 
own peculiar course, may undergo its own peculiar 
changes, without the fate of the cell lying next it being 
necessarily linked with its own. In other tissues, on the 
contrary, in which we find intermediate substance, every 
cell, in addition to its own contents, has the superin- 
tendence of a certain quantity of matter external to it, 
and this shares in its changes, nay, is frequently affected 
even earlier than the interior of the cell, which is ren- 
dered more secure by its situation than the external 
intercellular matter. Finally, there is a third series of 
tissues, in which the elements are more intimately con- 
nected with one another. A stellate cell, for example, 
may anastomose with a similar one, and in this way a 
reticular arrangement may be produced, similar to that 
which we see in capillary vessels and other analogous 
structures. In this case it might be supposed that the 
whole series was ruled by something which lay who 
knows how far off; but upon more accurate investiga- 
tion, it turns out that even in this chainwork of cells a 
certain independence of the individual members prevails, 
and that this independence evinces itself by single cells 


CELLULAR PATHOLOGY. 43 


undergoing, in consequence of certain external or internal 
influences, certain changes confined to their own limits, 
and not necessarily participated in by the cells imniedi- 
ately adjoining. | 

That which I have now laid before you will be suffi- 
cient to show you in what way I consider it necessary to 
trace pathological facts to their origin in known histolo- 
gical elements; why, for example, I am not satisfied 
with talking about an action of the vessels, or an action 
of the nerves, but why I consider it necessary to bestow 
attention upon the great number of minute parts which 
really constitute the chief mass of the substance of the 
body, as well as upon the vessels and nerves. It is not 
enough that, as has for a long time. been the case, the 
muscles should be singled out as being the only active 
elements ; within the great remainder, which is generally 
regarded as an imert mass, there is in addition an enor- 
mous number of active parts to be met with. 

Amid the development which medicine has undergone 
up to the present time, we find the dispute between the 
humoral and solidistic schools of. olden times still main- 
tained. The humoral schools have generally had the 
greatest success, because they have offered the most con- 
venient explanation, and, in fact, the most plausible 
interpretation of morbid processes. We may say that 
nearly all successful practical, and noted hospital, physi- 
cians have had more or less humoro-pathological tenden- 
cies ; aye, and these have become so popular, that it is 
extremely difficult for any physician to free himself from 
them. The solido-pathological views have been rather 
the hobby of speculative inquirers, and have had their 
origin not so much in the immediate requirements of / 
pathology, as in physiological and philosophical, and 
even in religious speculations. They have been forced 
to do violence to facts, both in anatomy and physiology, 


44. LECTURE I. 


and have therefore never become very widely diffused. 
According to my notions, the basis of both doctrines is 
an incomplete one; I do not say a false one, because it 
is really only false in its exclusiveness; it must be 
reduced within certain limits, and we must remember 
that, besides vessels and blood, besides nerves and ner- 
vous centres, other things exist, which are not a mere 
theatre (Substrat) for the action of the nerves and blood, 
upon which these play their pranks. 

Now, if it be demanded of medical men that they give 
their earnest consideration to these things also; if, on 
the other hand, it be required that, even among those 
who maintain the humoral and neuro-pathological doc- 
trines, attention at last be paid to the fact, that the blood 
is composed of many:single, independent parts, and that 
the nervous system is made up of many active individual 
constituents—this is, indeed, a requirement which at the 
first glance certainly offers several difficulties. But if 
you will call to mind that for years, not only in lectures, 
but also at the bedside, the activity of the capillaries 
was talked about—an activity which no one has ever 
seen, and which has only been assumed to exist in com- 
pliance with certain theories—you will not find it unrea- 
sonable, that things which are really to be seen, nay are, 
not unfrequently, after practice, accessible even to the 
unaided eye, should likewise be admitted into the sphere 
of medical knowledge and thought. Nerves have not 
only been talked about where they had never been 
demonstrated ; their existence has been simply assumed, 
even in parts in which, after the most careful investiga- 
tions, no trace of them could be discovered, and activity 
has been attributed to them in parts where they abso- 
lutely do not penetrate. It is therefore certainly not 
unreasonable to demand, that the greater part of the 
body be no longer entirely ignored ; and if no longer 


GROWTH OF PLANTS. 45 


ignored, that we no longer content ourselves with merely 
regarding the nerves as so many wholes, as a simple, 
indivisible apparatus, or the blood as a merely fluid ma- 
terial, but that we also recognise the presence within the 
blood and within the nervous system of the enormous 
mass of minute centres of action. 


In conclusion, I have still some preparations to ex- 
plain, and will begin with a very common object (Fig. 7). 
It has been taken from the tuber of a potato, at a spot 
where. you can view in its pefection 
the structure of a vegetable cell, 
where the tuber, namely, is begin- 
ning to put forth a new shoot, and 
there is, consequently, a probability 
of young cells being found, at least, 
if we suppose that all growth con- 
sists in. the development of new 
cells. In the interior of the tuber 
all the cells are, as is well known, stuffed full with 
granules of starch; in the young shoot, on the other 
hand, the starch is used up, in proportion to the growth, 
and the cell is again exhibited in its more simple form. 
In a transverse section of a young sprout near its exit 
from the tuber, about four different layers may be dis- 
tinguished—the cortical layer, next a layer of larger, 
then a layer of smaller, cells, and lastly, quite on the 
inside, a second layer of larger cells. Here we see 
nothing but regular structures ; thick capsules of hex- 





Fig. 7. From the cortical layer of a tuber of solanum tuberosum, after treatment 
with iodine and sulphuric acid. a. Flat cortical cells, surrounded by their capsule 
(cell-wall, membrane). 0. Larger, four-sided cells of the same kind from the cam- 
bium; the real cell (primordial utricle), shrunken and wrinkled, within the capsule. 
e. Cells with starch-granules lying within the primordial utricle. 


46 LECTURE I. 


agonal form, and within them one or two nuclei (Fig. 1). | 
Towards the cortex (corky layer) the cells are four-sided, 
and the farther one proceeds outwards, the flatter do 
they become ; still, nuclei may be distinctly recognised 
in them also. Wherever the so-called cells come in con- 
tact, a boundary line may be recognised between them ; 
then comes the thick layer of cellulose, in which fine 
streaks may be observed; and in the interior of the 
capsular cavity you see a compound mass, in which a 
nucleus and nucleolus may be easily distinguished, and 
after the application of reagents the primordial utricle 
also makes its appearance as a plicated, wrinkled mem- 
brane. This is the perfect form of a vegetable cell. In 
the neighbouring cells lie a few larger, dimly lustrous, 
laminated bodies, the remains of starch (Fig. 7,c). The 
next object is of importance in my eyes, because I shall 
afterwards have to refer to it when instituting a com- 
parison with new formations in animals. It is a longi- 
tudinal section of a young lilac bud, developed by the 
warm days we have had this month (February). In the 
bud a number of young leaves have already begun to 
develop themselves, each composed of numerous young 
cells. In these, the youngest parts, the external layers, 
are composed of tolerably regular layers of cells, which 
have a rather flat, four-sided appearance, whilst in the 
internal layers the cells are more elongated, and in a 
few parts spiral vessels show themselves. Especially 
would I call your attention to the little out-growths 
(leaf-hairs—Blatthaare), which protrude everywhere 
along the border, and very much resemble certain ani- 
mal excrescences, é. g., in the villi of the chorion, where 
they mark the spots at which young, secondary villi 
will shoot out. In our preparation, you see the little 
club-shaped protuberances, which are repeated at cer- 


GROWTH OF PLANTS. 47 


tain intervals and are connected internally with the 
rows of cells in the cambium. They are structures in 
which the more delicate forms of cells can best be 
distinguished, and, at the same time the peculiar mode 
of growth be discovered. ~ sy 

This growth is effected thus: : Fia. 8. 

a division takes place in 
some of the cells, and a 
transverse septum is formed ; 
the newly-formed parts con- 
tinue to grow as indepen- 
dent elements, and gradu- 
ally increase in size. Not 
unfrequently divisions take 
place also longitudinally, so 
that the parts.become thicker 
(Fig. 8, c). Every protu- 
berance is therefore origi- 



















ININISNESS 


| y} YY 
MG ty 


} 
= 
WZ t 
ae 
b} W v 
EP NIG ¢ 







Ess 
SS eS 
eeettrnry 
SSSNANESS 















SS 
———— Ss = 
S eer ~~ 
K MIEN. = 
: —— SUR 
SS 






YAY 
. . UY Fn! it 

nally a single cell, which, by aoesal || De 
continual subdivison in a Zp OS LrUG 
transverse direction (Fig. 8, Pe Ba UG i; 
Ap ebay 2 away his 
a, 6), pushes its divisions for- AO a AMA 
nee 


wards, and then, when occa- 
sion offers, spreads out also 
in a lateral direction. In this way the hairs shoot out, 
and this is in general the mode of growth, not only in 
vegetables, but also in the physiological and pathologi- 
cal formations of the animal body. 


Fig. 8. Longitudinal section of a young February-shoot from the branch of a 
syringa. A. The cortical layer and cambium; beneath a layer of very flat cells are 
seen larger, four-sided, nucleated ones, from which, by successive transverse divi- 
sion, little hairs (a) shoot out, which grow longer and longer (4), and, by division in 
a longitudinal direction (c), thicker. B. The vascular layer, with spiral vessels, 
@. Simple, four-sided, oblong, cortical cells.—Growth of Plants. 


48 LECTURE I. 


In the following preparation—a piece of costal carti- 
lage, in a state of morbid growth—changes are evident 
even to the naked eye, namely, little protuberances upon 
the surface of the cartilage. Cor- 
responding to these the microscope 
shows a proliferation of cartilage- 
cells, and we find the same forms 
as in the vegetable cells; large 
' groups of cellular elements, each 
of which has proceeded from a 
single previously existing cell, 
arranged in several rows, and dif- 
fering from proliferating vegetable 
cells only in this—that there is 
intercellular substance between the individual groups. 
In the cells we can as before distinguish the external 
capsule, which, indeed, in the case of many cells, is com- 
posed of two, three, or more layers, and within them 
only does the real cell come with its membrane, contents, 
nucleus, and nucleolus. 

In the following object you see the young ova of a 
frog, before the secretion of the yolk-granules has begun. 
The very large ovum (Hizelle) (Fig. 10, C) contains a 
nucleus likewise very large, in which a number of little 
vesicles are dispersed—and tolerably thick, opaque con- 
tents, beginning, at a certain spot, to become granular 
and brown. Around the cell may be remarked the rela- 
tively thin, connective tissue of the Graafian vesicle, 
with a hardly visible layer of epithelium. In the neigh- 





Fig. 9. Proliferation of cartilage; from the costal cartilage of an adult. Large 
groups of cartilage-cells within a common envelope (wrongly so-called parent- 
cells), produced from single cells by successive subdivisions. At the edge, one of 
these groups has been cut through, and in it is seen a cartilage-cell invested by a 
number ef capsular layers (external secreted masses). 300 diameters. 


LARGE AND SMALL ANIMAL CELLS. 49 


bourhood are lying several smaller ova, which show the 
gradual progress of their growth. 





As a contrast to these gigantic cells, I place before 
you an object from the bed-side ; cells from 
fresh catarrhal sputa. You see cells incom- 4 
parison very small, which with a higher power, @ ‘a 
prove to be of a perfectly globular shape, and, @ 
in which, after the addition-of water and re- “@ ; 
agents, a membrane, nuclei, and, when fresh, 
cloudy contents can clearly be distinguished. Most of 


Fig. 11. 


Fig. 10. Young ova from the ovary of afrog. A. A very young ovum. B. 
A larger one. (. A still larger one, with commencing secretion of brown granules 
at one pole (e), and shrunken condition of the vitelline membrane from the imbi- 
bition of water. a. Membrane of the follicle. 6. Vitelline membrane. ec. Mem- 
brane of the nucleus. d. Nucleolus. S. Ovary. 150 diameters. 

Fig. 11. Cells from from fresh catarrhal sputa. .A. Pus-corpuscles. a. Quite 
fresh. 5. When treated with acetic acid. Within the membrane the contents 
have cleared up, and three little nuclei are seen. .B. Mucus-corpuscles. a, A sim- 


ple one. 6%. Containing pigment granules. 300 diameters. 
4 


50 LECTURE I. 


the small cells belong, according to the prevailing termi- 
nology, to the category of pus-corpuscles ; the larger 
ones, which we may designate mucus-corpuscles or ca- 
tarrhal cells, are partly filled with fat or greyish-black 
pigment, in the form of granules. 

These structures, however small their size, possess all 
the typical peculiarities of the large ones ; all the charac- 
ters of a cell displayed by the large ones again present 
themselves in them. But this is, in my opinion, the 
most essential point—that, whether we compare large or 
small, pathological or physiological, cells, we always find 
this correspondence between them. 








LB OPW BR Wesdiks 


FEBRUARY 17, 1858. 


~PHYSIOLOGIOAL TISSUES. 


Falsity of the view that tissues and fibres are made up of globules (elementary 
granules)—The investment theory (Umhiullungstheorie)—Equivocal [spontane- 
ous] generation of cells—The law of continuous development. 

General classification of the tissues—The three categories of General Histology— 
Special tissues—Organs and systems, or apparatuses. 

The Epiraettat Tissues—Squamous, cylindrical, and transitional epithelium— 
Epidermis and rete Malpighii—Nails, and their diseases—Crystalline lens— 
Pigment—Gland-cells. 

The Connective Tissues—The theories of Schwann, Henle, and Reichert—My 
theory—Connective tissue as intercellular substance—Cartilage (hyaline, fibro- 
and reticular)—Mucous tissue—Adipose tissue--Anastomosis of cells; juice- 
conveying system of tubes or canals, 


In my first lecture, gentlemen, I laid before you the 
general points to be noted with regard to the nature and 
origin of cells and their constituents. Allow me now to 
preface our further considerations with a review of the 
animal tissues in general, and this both in their physio- 


logical and pathological relations. 


The most important obstacles which, until quite 
recently, existed in this quarter, were by no means 
chiefly of a pathological nature. I am convinced that 
pathological conditions would have been mastered with 
far less difficulty if it had not, until quite lately, been 
utterly impossible to give a simple and comprehensive 


sketch of the physiological tissues. The old iets 


52 LECTURE II. 


which have in part come down to us from the last cen- 
tury, have exercised such a preponderating influence 
upon that part of histology which is, in a pathologi- 
cal point of view, the most important, that not even yet 
has unanimity been arrived at, and you will therefore 
be coustrained, after you have inspected the prepara- 
tions I shall lay before you, to come to your own con- 
clusions as to how far that which I have to communicate 
to you is founded upon real observation. 

If you read the ‘ Elementa Physiologiaw’ of Haller, you 
will find, where the elements of the body are treated of, 
the most prominent position in the whole work assigned 
to fibres, the very characteristic expression being there 
made use of, that the fibre (fibra) is to the physiologist 
what the line is to the geometrician. 

This conception was soon still further expanded, and the 
doctrine that fibres serve as the groundwork of nearly all 
the parts of the body, and that the most various tissues 
are reducible to fibres as their ultimate constituents, 
was longest maintained in the case of the very tissue in 
which, as it has turned out, the pathological difficulties 
were the greatest—in the so-called celluiar tissue. 

In the course of the last ten years of the last century 
there arose, however, a certain degree of reaction against 
this fibre-theory, and in the school of natural philoso- 
phers another element soon attained to honour, though 
it had its origin in far more speculative views than the 
former, namely, the globule. Whilst some still clung to 
their fibres, others, as in more recent times Milne 
Edwards, thought fit to go so far as to suppose the 
fibres, in their turn, to be made up of globules ranged 
in lines, This view was in part attributable to optical 
illusions in microscopical observation. The objection- 
able method which prevailed during the whole of the 
last and a part of the present century—of making obser- 





; 





ELEMENTARY FIBRES AND GLOBULES. 538 


vations (with but indifferent instruments) in the full 
glare of the sun—caused a certain amount of dispersion 
of light in nearly all microscopical objects, and the 
impression communicated to the observer was, that he 
saw nothing else than globules. On the other hand, 
however, this view corresponded with the ideas common 
amongst natural philosophers as to the primary origin 
of everything endowed with form. 

These globules (granules, molecules) have, curiously 
enough, maintained their ground, even in modern histo- 
logy, and there are but few histological works which do 
not begin with the consideration of elementary granules. 
In a few instances, these views as to the globular nature 
of elementary parts have, even not very long ago, ac- 
quired such ascendancy, that the composition, 
both of the primary tissues in the embryo and 
also of the later ones, was based: upon them. A 


Fia. 12. 


cell was considered to be produced by the 
globules arranging themselves in a spherical 
form, so as to constitute a membrane, within 
which other globules remained, and formed the contents. 
In this way did even Baumgartner and Arnold contend 
against the cell theory. 

This view has, in a certain manner, found support 
even in the history of development—in the so-called 
investment-theory (Umbhiillun gstheorie)—a doctrine which 
for a time occupied a very promi- 
nent position. The upholders of Fig. 13, 
this theory imagined, that origi- 
nally a number of elementary 
globules existed scattered through 





Fig. 12. Diagram of the globular theory. a. Fibre composed of elementary 
granules (molecular granules) drawn up ina line. 6. Cell with nucleus and spheri- 


cally arranged granules. 
Fig. 18. Diagram of the investment- (cluster-) theory. a. Separate elementary 


54 LECTURE II. 


a fluid, but that, under certain circumstances, they 
gathered together, not in the form of vesicular mem- 
branes, but so as to constitute a compact heap, a globe 
(mass, cluster—Kliimpchen), and that this globe was the 
starting point of all further development, a membrane 
being formed outside and a nucleus inside, by the diffe- 
rentiation of the mass, by apposition, or intussusception. 

At the present time, neither fibres, nor globules, nor 
elementary granules, can be looked upon as histological 
starting-points. As long as living elements were con- 
ceived to be produced out of parts previously destitute 
of shape, such as formative fluids, or matters (plastic 
matter, blastema, cytoblastema), any one of the above 
views could of course be entertained, but it is in this 
very particular that the revolution which the last few 
years have brought with them has been the most 
marked. JHven in pathology we can now go so far as to 
establish, as a general principle, that no development of 
any kind begins de novo, and consequently as to reject 
the theory of equivocal [spontaneous] generation just as 
much in the history of the development of individual parts 


_as we do in that of entire organisms. Just as little as 


we can now admit that a teenia can arise out of saburral 
mucus, or that out of the residue of the decomposition 
of animal or vegetable matter an infusorial animalcule, a 
fungus, or an alga, can be formed, equally little are we 
disposed to concede either in physiological or pathologi- 
cal histology, that a new cell can build itself up out of 
any non-cellular substance. Where a cell arises, there a 
cell must have previously existed (omnis cellula e cellula), 
just as an animal can spring only from an animal, a 
plant only from a plant. In this manner, although there 


granules. 6, Heap of granules (cluster). c. Granule-cell, with membnene and 
nucleus. a Ai 


ooo" 








LAW OF CONTINUOUS DEVELOPMENT. 55 


are still a few spots in the body where absolute demon- 
stration has not yet been afforded, the principle is 
nevertheless established, that in the whole series of 
living things, whether they be entire plants or animal 
organisms, or essential constituents of the same, an 
eternal law of continuous development prevails. There is 


no discontinuity of development of such a kind that a | 
new generation can of itself give rise to a new series of | 


developmental forms. No developed tissues can be 
traced back either to any large or small simple element, 
unless it be unto a cell. In what manner this continuous 
proliferation of cells (Zellenwucherung), for so we may 
designate the process, is carried on, we will consider 
hereafter ; to-day, my especial object only was to deter 
you from assuming as the groundwork of any views you 
might entertain with regard to the composition of the 
tissues, these theories of simple fibres or simple globules 
(elementary fibres or elementary globules).— 

If it be wished to classify the normal tissues, a very 
simple point of view, founded upon marked characteris- 
tics, offers itself, upon which their division into three 
categories may be based. 

We either have tissues which consist exclusively of 
cells, where cell lies close to cell—in fact, cellular tissue 


in the modern sense of the word—or we find tissues, in 


which one cell is regularly separated from the other by a 
certain amount of intermediate matter (intercellular 
substance), and, therefore, a kind of uniting medium 
exists, which, while it. visibly connects the individual 
elements, yet holds them separate. To this class belong 
the tissues which are now-a-days generally comprehended 
under the name of connective tissues (Gewebe der Bin- 
desubstanz), and of which what was formerly universally 
called cellular tissue constitutes the chief portion. 
Finally, there is a third group of tissues, in which the 


56 LECTURE IL. 


cells have attained specific, higher forms of development, 
by means of which their constitution has acquired a 
type entirely peculiar ; indeed, in part so peculiar, as to 
appertain exclusively to the animal economy. These are 
the tissues which are really characteristic of animals, 
although a few among them exhibit transitions of vege- 
table forms. To this class belong the nervous and 
muscular systems, the vessels and the blood. Herewith 
is the list of tissues concluded. 

You must now proceed to consider, in what respect, 
in this summary of the result of histological researches, 
a contrast is afforded to what was formerly, chiefly in 
imitation of Bichat, regarded as constituting a tissue. 
Bichat’s tissues would, for the most part, not so much 
represent what we now regard asthe subjects of General 
Histology, as what we must rather designate as_be- 
longing to Special Histology. For, if we regard the 
tissues in the light they were formerly regarded ; if we, 
for example, separate tendons, bones, and facie, from 
one another, we then obtain an extraordinary variety 
of categories (Bichat had twenty-one), but there are 
not quite as many simple forms of tissue to correspond 
to them. 

In accordance with modern notions, the whole domain 
of anatomy should first be divided into the categories of 
General Histology (¢zsswes properly so called). Special 
Histology, then, takes up the instances, in which a com- 
bination of tissues, sometimes very different, into a 
single whole (organ) takes place. Thus we speak, for 
example, of osseous tissue; but this tissue, the tela 
ossea of general histology, does not of itself form bone, 
for no bone consists entirely of tela ossea, but it has 
necessarily superadded at least periosteum and vessels. 
Nay, and from this simple conception of a bone, every 
bone of considerable size, for example, a long bone, 





EPITHELIAL FORMATIONS, 57 


differs ; for that is a real organ, in which we can distin- 
guish at least four different tissues. We have in it the 
tela ossea properly so called, the cartilaginous layer, the 
stratum of connective tissue belonging to the periosteum, 
and the peculiar medullary tissue. These several parts 
again are exceedingly heterogeneous in their nature, 
inasmuch as, for example, vessels and nerves enter into 
the composition of the marrow, the periosteum, etc, All 
these must be taken together to constitute the entire 
organism of a bone. Before we come, therefore, to 
systems or apparatuses, properly so called, the special 
subject of descriptive anatomy, a long series of grada- 
tions must be traversed, and,in discussions we must 
always begin by having a clear idea of what the question 
is. When bone and osseous tissue are confounded to- 
gether, the extremest confusion is occasioned, and so also 
when it is sought to identify nervous with cerebral 
_ matter. The brain contains many things which are not 
of a nervous nature, and its physiological and pathologi- 
cal conditions cannot be comprehended if they are 
regarded as occurring in an aggregation of purely ner- 
vous parts, and no consideration is paid to the membranes, 
the interstitial substance, and the vessels, as well as the 
nerves. | 

If, now, we consider the first of the classes into which 
_ we have divided General Histology, namely, the simple 
cellular tissues, a little more attentively, we find that 
those of which we can best obtain a general idea are 
unquestionably the epithehal formations, such as we meet 


with in the epidermis and the rete Malpighii, upon the ,)/), 


external surface of the body, and in the cylindrical and 
scaly epithelium of mucous and serous membranes. 
Their general plan is, that cell lies close to cell, so that 
in the most favorable specimens, as in plants, four- or 
six-sided cells lie in immediate apposition one to the 


58 LECTURE II. 


other, and nothing at all is found between them. The 
same is the case in many places with the scaly or pave- 
ment-epithelium (Fig. 16). These forms are evidently 
in a great measure due to pressure. For all the elements 
of acellular tissue to possess perfect regularity of form, it 
is requisite that they should all grow in a perfectly uni- 
form manner, and simultaneously. If their development 
takes place under circumstances such that less resistance 
is offered in one direction, it then may come to pass 
_ that, as in the case of columnar or cylindrical epithelium, 
the cells will shoot out in this one direction and become 
very long, whilst in the other direction they remain very 
* narrow. But even one of 
these cells, when seen in - 
transverse section, will pre- 
ent an hex agonal shape, 
and if we look down upon 
the free surface of cylindri- 
cal epithelium, we see in it, 
too, regularly polygonal forms (Fig. 14, 0). 

Contrasting with these, singularly irregular forms are 
met with in places where the cells shoot up in an irregu- 
lar manner, and accordingly they are found with remark- 
able constancy on the surface of the urinary passages, in 
their whole extent from the calyces of the kidneys down 
to the urethra. In all these parts it is very common to 
meet with instances in which a cell is round at one end, 
whilst at the other it terminates in a point, or where it 
exhibits the appearance of a somewhat thick spindle, or is 


Fig. 14. 





Fig. 14. Columnar or cylindrical epithelium from the gall-bladder. a. Four con- 
tiguous cells seen in profile, each with a nucleus and nucleolus, their contents 
slightly marked with longitudinal striae; along the free (upper) edge, a thickish 
border, marked with fine, radiated lines. 6. Similar cells, with their free (upper, 
outer) surface seen obliquely, so as to show the hexagonal form of a transverse 
section, and their thick border. c. Cells altered by imbibition, somewhat swollen 
up and with the upper border split into fibrils. 


EPIDERMIS. 59 


slightly rounded on one side and excavated on the other, 
or where a cell is so thrust in between others as to assume 
a clubbed or jagged form. 
But in these cases also the 
one cell always corresponds 
with the other in form, and 
it is not any peculiarity in 
the cell which gives rise to 
its shape, but the way in 
which it lies, its relations 
to the neighbouring cells, 
and its having to adapt 
itself to the arrangement of the parts next to it. In 
the direction of the least resistance the cells acquire 
points, jaggs and projections of the-mest manifold descrip- 
tion. As they did not well admit of classification, Henle 
gave them the name, which has since been adopted, of 
transitional epithelium, to express their gradual transi- 
tion into distinct scaly and cylindrical epithelium. Some- 
times, however, this is not the case, and another name 
for them might just as well have bien adopted. 

On account of the importance of the subject, I will 
just add a few words with regard to the cuticle (epider- 
mis). In this it fortunately happens that, what is not 
the case in many mucous membranes, many layers of 
cells lie one above the other, and that the young layers 
(the rete Malpightt [mucosum]) can easily and con- 
veniently be separated from the older ones (the epider- 


mis proper). 


Fie. 15. 





Fig. 15. Transitional epithelium from the urinary bladder. a. A large cell, with 
excavations along its border, into which more delicate club- and spindle-shaped 
cells fit. %. The same; the larger cell with two nuclei. ec. A larger, irregularly 
angular cell, with four nuclei. d. A similar cell, with two nuclei and nine depres- 
sions, as seen from above, corresponding to the excavations of the border. (Comp. 
‘ Archiv. fiir path. Anat. und Phys.,’ vol iii., plate i., fig. 8.) 


60 LECTURE II. 


On examining a perpendicular section of the surface 
of the skin, we for the most part see externally a very 
dense stratum, of variable thickness, which at the first 
glance is discovered to consist of nothing but flattened 
cells, that, when viewed edgeways, look like lines. 
They might be taken for fibres, piled up one above the 
other, and with slight differences of level making up the 
the whole external layer. Beneath these layers we find, 


..~differing in thickness and substance, the so-called rete 


Malpighii, and next to this, in a downward direction, 
the papille of the skin. If, now, we examine the 
boundary between the epidermis and the rete, the result 
we obtain by nearly every method of examination is, 





Fig. 16. Perpendicular section through the surface of the skin of a toe, treated 
with acetic acid. P. P. Extremities of cut papillae, in each of which a vascular loop, 


NAILS. 61 


that to the innermost layer of the epidermis, very closely 
and almost abruptly, there succeed cells, which at first 
are also flattened, but in a less degree, and within which 
very distinct nuclei may be distinguished. These tole- 
rably large cells mark the transition from the oldest 
layers of the rete Malpighii to the youngest of the epi- 
dermis. This is the point from which proceeds the re- 
generation of the epidermis, in itself an inert mass,which 
is gradually removed from the surface. And here is 
also generally the boundary, at which pathological pro- 
cesses set in. . The farther we advance inwards, the 
smaller do the cells become ; the last of them standing 
in the form of little cylinders upon the surface of the 
papille (Fig. 16 7, r). 

On the whole, the relations’ of the individual parts 
throughout the whole surface of the skin are everywhere 
the same, however manifold the peculiarities of detail 
may be, which the individual layers offer in respect to 
thickness, position, firmness, and connection. A section 
of a nail, for example, which in its external appearance 
certainly widely differs from ordinary epidermis, pre- 
sents, nevertheless, on the whole, the same conformation, 
and has only one essentially distinctive feature, that, 
namely, in it two different epidermoidal structures are 
thrust, the one over the other, and thus a complication 
arises, which, if not duly attended to, may lead to the 
assumption of certain specific differences between it and 
other parts of the epidermis, whilst it really consists only 
in a peculiar change in the position of certain layers of 


and near it little spindle-shaped, connective-tissue corpuscles, displaying at the base 
a reticulated arrangement, may be observed; to the left, a bulging out of the pa- 
pilla, corresponding to a tactile corpuscle, no longer visible, and situated at a 
deeper level. R. R. The rete Malpighii; immediately around the papilla a very 
dense layer of small, cylindrical cells (r, r); more externally, polygonal cells, gra- 
dually increasing in size. ZH. Epidermis, consisting of flat and more closely packed 
layers of cells. S S. Duct of a sweat gland passing through. 300 diameters. 


69 LECTURE I. 


the epidermis with regard to one another. The extremely 
dense and hard scales, which constitute the uppermost 
part, the so-called body of the nail (Nagelblatt), may, by 
different methods, be restored to forms in which they 
present the ordinary appearances of cells, and this is 
best seen after treatment with an alkali, when every 
scale swells up into a large, broadly oval, cell. 

In the uppermost layers of the epidermis the cells be- 
come everywhere flatter, and towards the external surface 
no more nuclei at all can be discovered in them. Still 
there is no original difference between the epidermis and 
the rete Malpighii; the latter is only the matrix of the 
epidermis, or indeed its youngest layer, inasmuch as 
from it there is a constant apposition of new parts tak- 
ing place, which gradually become flatter and flatter, and 
move upward as fast as the scales on the outside disap- 
pear through friction of the surface, washing, or rubbing. 
But between the lowest layer of the rete and the sur- 
face of the cutis vera there are no intervening layers ; 
there is no amorphous fluid or blastema to be found 
there in which the cells could be generated, but they lie 
indirect contact with the papillee of connective tissue of 
the cutis. There is therefore nowhere any space here, 
as there was thought to be even a short time ago, into 
which fluid transudes from the papille and the vessels 
contained therein, in order that new cells may arise and 
develop themselves out of it. Ofsucha fluid there is 
absolutely nothing discernible, but throughout the whole 
series of the layers of cells of the rete and epidermis the 
same relations exist that we are familiar with in the 
bark of a tree. The cortical layer of a potato (Fig. 7) 
exhibits in a similar manner, externally, corky, epider- 
moidal cells, and underneath, as in the rete Malpighii, a 
layer of nucleated’ cells, the cambium, constituting the 
matrix for the subsequent growth of the cortex. 


& 


NAILS. 63 


Very much the same is the case with the nails. On 
examining the section of a nail, made transversely to the 
long axis of the finger, we see virtually the same struc- 
ture as in ordinary skin, only every single indentation of 
the inferior surface does not correspond to a conical 
prolongation of the cutis, or papilla, but to a ridge which 
runs along the entire length of the bed of the nail, and 
may be compared with the ridges which are to be seen 
upon the palmar surface of the fingers. Upon these 
ridges of the bed of the nail are dwarfish, stunted papillae, 
and upon them rests the rather cylindrically shaped 
youngest layer of the rete Malpighii; then follow cells 
continually increasing in size, until at last the really 
hard substance comes, which corresponds to the epi- 
dermis. ° 

Nevertheless—to discuss the subject at once, seeing 
that I shall not again have occasion to mention it—the 
structure of the nails has been difficult to make out, 
because they were conceived to be a simple formation. 
Nearly all the discussions, therefore, which have taken 
place, have turned upon the question where the matrix 
of the nail was, and whether the growth of the latter 
took place from the whole surface or from the little fold 
into which it is received behind. If we consider the nail 
with respect to its proper firm substance, its compact 
body (Nagelblatt), this only grows from behind, and is 
pushed forwards over the surface of the so-called bed of 
the nail (Nagelbett), but this in its turn also produces a 
definite quantity of cellular elements, which are to be 
regarded as the equivalents of an epidermic layer. On 
making a section through the middle of a nail, we come, 
most externally, to the layer of nail which has grown 
from behind, next to the substance which has been 
secreted by the bed of the nail, then to the rete Malpi- 
ghii, and lastly to the ridges upon which the nail rests. 


« 


84 LECTURE II. 


Thus the nail lies in a certain measure loose, ard can 
easily move forwards, pushing itself over a moveable 
substratum, while it is kept in place by the ridges with 
which its bed is beset. When a section is made trans- 
versely through a nail, we see, as already mentioned, 
essentially the same appearance presented as that offered 
by the skin, only that a long ridge corresponds to every 
single papilla seen in ordinary sections of the skin ; the 
undermost part of the nail has slight indentations cor- 
responding to these ridges, so that, while gliding along 
over them, it can execute lateral movements only within 
certain limits. In this manner, the body of the nail 
which grows from behind moves forwards over a cushion 
of loose epidermic substance (Fig. 17, @) in grooves 
which are provided by the ridges and furrows of the bed 
of the nail. The uppermost part of the nail, if examined 
when fresh, is composed of so dense a substance that it 
is scarcely possible to distinguish individual cells in it 
without applying reagents, and at many points an 
appearance is presented like that which we see in car- 
tilage. But by treating it with potash, we can convince 
ourselves that this substance is composed of nothing but 
epidermis-cells. From this mode of development you 
will see how easily intelligible distinctions may be drawn 
between the different diseases of the nails. 

There are diseases of the bed of the nail which do not 
affect the growth of its body, but may give rise to 
changes in its position. When there is a very abun- 
dant development of cells in the bed of the nail, the body 
may be pushed upwards (Fig. 17, 6); nay, it sometimes 
happens that the nail, instead of growing horizontally, 
shoots perpendicularly upwards, the space underneath 
being filled with a thick accumulation of the loose 
cushiony substance (Polstermasse) (Fig. 17, c). Thus 
suppuration may take place in the bed of the nail with- 


CRYSTALLINE LENS 65 


out the development of its body being thereby impeded. _ 


The most singular changes occur in small pox. When 
a pock forms upon the bed of the 
nail, there is nothing to be seen 
but a yellowish, somewhat uneven, 
spot ; but if, on the other hand, 
it is developed upon the fold, then 7 
its traces are left in the shape of amt 
a circularly depressed, and, as it 
were, excavated spot in the body 
of the nail as it gradually advances, 
a proof of a loss of substance pre- 
cisely similar to that which takes 
place in the epidermis. 

I will not to-day, gentlemen, 
enter more particularly into the spe- 
cial history of the formation of epi- 
dermis and epithelium, although it is of great importance 
for the right comprehension of many pathological pro- 
cesses, but content myself with calling your attention to 


Fie. 17. 





the fact, that, under particular circumstances epithelial _ 


cells may undergo a series of transformations, through 
which they become extremely unlike what they originally 


were, and gradually assume appearances which render it 


impossible for those who are unacquainted with the history 
of their development to realize their original epidermic 
nature. The greatest abnormity of the kind is met with 
in the crystalline lens of the eye, which is originally a mere 


Fig. 17. Diagrammatic representation of a longitudinal section of a nail. a. The 
normal condition ; a gently curved, horizontal nail, implanted in its fold, and sepa- 
rated from its bed by a thin cushion. 6. A more markedly curved and somewhat 
thicker nail, with great thickening of the cushion, and much increased curvation 
of the bed, the fold being shorter and wider. ¢. Onychogryphosis; the nail, short 
and thick, reared up at a considerable angle, the fold short and wide, the bed fur- 
rowed on its surface, the cushion very thick and composed of layers of loose cells, 
piled up one above the other. 

5 


66 LECTURE II. 


_ accumulation of epidermis. It has its origin, as is well 
known, in a saccular involution of the external skin. At 
first its connection with the external parts continues to 
be maintained by means of a delicate membrane, the 
membrana capsulo-pupillaris; afterwards this atrophies 
and leaves the lens isolated in the interior of the eye. 
The fibres of the lens are therefore, as C. Vogt has 
shown, nothing more than epidermoidal cells which have 
been developed in a peculiar manner, and their regene- 
ration, after the extraction of a cataract for example, is 
only possible as long as there still remains epithelium in 
the capsule to undertake the new formation, and to 
represent, as it were, a thin layer of rete Malpighii. 
This reproduces the lens in the same way that the ordi- 
nary rete Malpighii of the external surface does the 
cuticle. Amongst the other changes of epithelial struc- 
tures we shall in due time revert to the peculiar pig- 
ment cells that are produced in the most different parts 
by the direct transformation of epidermic cells, the con- 
tents of which either become coloured by imbibition, or 
have pigment engendered in them by a (metabolic) 
transposition of their elements. 

With the history of epithelial elements properly so 
called is immediately connected that of a peculiar class 
of structures which play a very important part in the 
accomplishment of the functions of an animal, namely 
the glands. The really active elements of these organs 
are essentially of an epithelial nature. One of Remak’s 
greatest merits consists in his having shown that in the 
normal development of the embryo the outer and inner 
of the well-known three layers of the germinal mem- 
brane chiefly produce epithelial structures, from a gra- 
dual proliferation of the elements of which glandular 
structures arise. Other observers, for example, Kélliker, 
had indeed before him made similar observations, but by 





GLANDS. 67 


Remak was first established the law that the formation . 


of glands in general must be regarded as consequent 
upon a direct process of proliferation on the part of 


epithelial structures. Previously large quantities of | ,. 
cytoblastema had been conceived to exist, in which, |, 
spontaneously, glandular substance took its rise ; but, with 


the exception of the lymphatic glands, and perhaps those 
belonging to the sexual organs, their mode of origin is 
everywhere this—that at a certain point, in a manner 
very similar to that which I described to you in the fore- 
going lecture, when speaking of the excrescences of 
plants, an epithelial cell begins to divide, and goes on 
dividing again and again, until by degrees a little process 
composed of cells grows inwards, and, spreading out 
laterally, gives rise to the development of a gland, which 
thus straightway consitutes a body continuous with lay- 
ers of cells originally external. Thus arise the glands of 
the surface of the body (the sudoriferous and sebaceous 
glands of the skin and the mammary gland), and thus 
also arise the internal glands of the digestive tract (the 
stomach glands and liver.) The most simple forms which 
glands can present do not occur at all in man. In infe- 


rior animals, however, wni-cellular glands have recently ~~ 


been discovered. The glands of the human body are 
invariably made up of a number of elements, which can, 
however, ultimately be traced back to a nearly simple 
type. Besides, in our own glands, in consequence of 
their size and complicated structure, other necessary 
constituents generally enter into their composition, so 
that, regarded as organs, they certainly do not consist of 
gland-cells only. But all parties are now pretty well 
agreed that the gland-cells are the really essential cle- 
ments, just as the primitive bundles are in muscle, and 
that the specific action of a gland is dependent upon the 
properties and peculiar arrangement of these elements. 


68 LECTURE II. 


Generally speaking, therefore, glands consist of accu- 
mulations of cells, which usually form open canals. With 


Fia. 18. 





the exception of the glands, whose functions are uncer- 
tain, such as the thyroid body and supra-renal capsules, 
there are in the human body only the ovaries which form 
an exception to this rule, inasmuch as their follicles are 
only open at times; yet they too must be open when 
the specific secretion of the ova has to take place. In 
most glands there is found indeed besides a certain quan- 
tity of transuded fluid, but this only constitutes the 
vehicle which floats off either the cells themselves, or 
their specific products. Suppose, for example, that in 
one of the ducts of the testicle a cell, in which there is 
a production of spermatozoa, becomes detached, then there 
transudes at the same time a certain quantity of fluid, 
which carries them away; but what makes the semen, 
semen, and constitutes the specific character of the action 


Fig. 18. A. Development of sweat-glands by means of the proliferation of the 
cells of the rete Malpighii in an inward direction. e. Epidermis. 1. Rete Malpighii. 
g g- Solid process, constituting the first rudiments of a gland. After Kolliker. 

B. Portion of the duct of the sweat-gland ina state of complete development. 
¢ ¢. Tunica propria. ee. Layers of epithelium. 


THEORIES RESPECTING CONNECTIVE TISSUE. 69 


is the peculiar power of the cell; the mere transuda- | 
tion from vessels is no doubt a means of conveyance 
onwards, but does not constitute the specific action of r 
the gland nor the real secretion. In an analogous man-— 
ner, in all the glands of which we can follow the action 
in all its details with precision, the essential peculi- 
arities of their energy are derived from the development 
and transformation of epithelial cells. 

The second histological group is formed by the con- 
nective tissues (Gewebe der Bindesubstanz). This is the ” 


subject in which I[ take the most interest, because it was» 


here that my own observations, which have led to the 
result to which I directed your attention at the begin- 
ning of these lectures, originated. The alterations which . 
I have succeeded in introducing in the views of histolo- 
_ gists with regard to the whole group have, at the same 
time, enabled me to give a certain degree of roundness 
and completeness to the cellular theory. 

Previously, connective tissue had nearly universally 
been regarded as essentially composed of fibres. On 
examining loose connective tissue in different re- 


gions, as, for example, beneath the corium, in the pia | ~ 


mater, subserous and submucous cellular tissue, we find” 
wavy bundles of fibres, the so-called wavy connective tts- 
sue (Fig. 19, A). This wavy character, which is inter- 
rupted at certain intervals, so as to give rise to a kind 
of fasciculation, could, it was thought, with the less hesi- 
tation be attributed to the presence of separate fibres, 
because at the end of each bundle isolated filaments 
could in reality be seen to protrude. In spite of this, 
however, an attack was made upon this very hypothesis, 
‘somewhat more than ten years ago, and has proved of 
very great importance, though in a manner different to 
to that which was intended. Reichert endeavoured, 
namely, to show that the fibres were only an optical 


(| a LECTURE II. 


illusion produced by folds, and that connective tissue in 
all parts formed a homogeneous mass, endowed with a 
great tendency to the formation of folds. 


Fia. 19. 











Schwann had, in reference to the formation of con- 
nective tissue, assumed that there originally existed spin- 
dle-shaped cells, the caudate corpuscles (geschwinzte 
Korperchen) (fibro-plastic corpuscles of Lebert), which 
afterwards became so famous ; and that out of these cells 
fasciculi of connective tissue were directly developed by 
the splitting up of the body of the cell into distinct fi- 
brils, whilst the nucleus remained as such (Fig. 19, B). 
Henle, on the other hand, thought the only conclusion 
his observations would warrant was, that there were 
originally no cells at all, but that nuclei only were 
formed in the blastema at certain intervals ; whilst the 


Fig. 19. A. Bundle of common, wavy, connective tissue (intercellular substance), 
splitting at its end into fine fibrils. 

B. Diagram of the development of connective tissue according to Schwann. a. 
Spindle-shaped cell (caudate corpuscle, fibro-plastic corpuscle of Lebert), with nu- 
cleus and nucleolus. 6. Cleavage of the body of the cell into fibrils. 

C. Diagram of the development of connective tissue, according to Henle. a. 
Hyaline matrix (blastema), with nucleolated nuclei regularly distributed through it. 
b. Fibrillation of the blastema (direct formation of fibrils), and transformation of 
the nuclei into nucleus-fibres. 


. THEORIES RESPECTING CONNECTIVE TISSUE. 71 


fibres, which afterwards appeared, were produced by a 


intermediate substance was thus being differentiated into 
fibres, the nuclei gradually became elongated, so as at 
length to run into one another, and thus give rise to 
peculiar longitudinal fibres, mucleus-fibres (Kernfasern) 
(Fig. 19, C). Reichert took an extremely important 
_ step in opposition to these views. He showed, namely, 

that originally there were only cells, and those in great 
abundance, between which intercellular substance was 


deposited. But the membrane of the cells became, he 
thought, at a certain period, blended with the intercel- - 


lular tissue, and then a stage was reached analogous to 
that described by Henle, in which there no longer ex- 
isted any boundary between the original cells and the 
intermediate substance. And, finally, he imagined that 
‘the nuclei, too, entirely disappeared in some instances, 
whilst they were preserved in others. On the other 
hand, he positively denied the occurrence of the spindle- 
shaped cells of Schwann, and declared all such, as well 
as the caudate and jagged cells, to be just as much 
artificial products as the fibres, which were said to be 
seen in the intervening substance, were a false interpre- 
tation of an optical image. | 

Now, my own investigations have shown, that both 
Schwann’s and Reichert’s observations,-up to a certain 
point, have some foundation in truth. That, in the first 
place, in opposition to Reichert, spindle-shaped and stel- 
late cells indisputably do exist (Fig. 20) ; and secondly, 
in opposition to Schwann, and with Reichert, that a 
direct splitting up of the cells into fibres does not take 


place, but that on the contrary, what is afterwards pre- | 
sented to our sight as connective tissue has really taken ~ 


the place of the previously homogeneous intercellular 
substance, I have found, moreover, that Reichert, 


direct fibrillation of the blastema; and that, whilst the ” 


19 LECTURE II. 


Henle, and Schwann, were wrong in maintaining that 
ultimately at best only nuclei or nucleus-fibres remained ; 


Fie. 20. 





and that, on the contrary, in most cases the cells them- 
selves preserve their integrity. The connective tissue 
of a later period is therefore not distinguished in its 
general structure and disposition in any respect from 
that of an earlier date. There is not an embryonic con- 
nective tissue with spindle-shaped cells and a perfectly 
developed one without them, but the ceils remain the 
same, although they are often not easy to see. 
Hssentially, therefore, this whole series of lower tis- 
sues may be reduced to one simple plan. Usually, the 
greater part of the tissue is composed of intercellular 
substance, in which, at certain intervals, cells lie imbed- 
ded, which in their turn present the most manifold forms. 
But these tissues cannot be distinguished by one’s con- 


Fig. 20. Connective tissue from the embryo of a pig, after long-continued boil- 
ing. Large spindle-shaped cells (connective-tissue corpuscles (Bindegewebskorper- 
chen)), some isolated, some still imbedded in the basis-substance, and anastomosing 
one with the other. Large nuclei, with their membrane detached ; cell-contents in 
some cases shrunken, 350 diameters. 


FORMATION OF CONNECTIVE TISSUE. 73 


taining only round, another’s, on the contrary, only 
caudate or stellate, cells. but in all connective tissues 


Fig. 21. 




















round, long and angular cells may occur. The simplest 
case is where round cells lie at certain intervals, and 
intercellular substance appears between them. This is 
the form which we see most beautifully shown in hyaline 
cartilage, as in that lining the joints, for example, in 
which the intercellular matter is perfectly homogeneous, 
and we see nothing but a substance which, though, per- 
haps, slightly granulated here and there, is on the whole 
quite as clear as water, so that as long as we do not see 
the edges of the preparation, doubt may arise as to whe- 
ther anything at all exists between the cells. 

This substance is characteristic of hyaline cartilage. 
Now we find that, under certain circumstances, the round 
cells became even in cartilage transformed into oblong 


Fig. 21. Diagram of the development of connective-tissue, according to my inves- 
tigations. .A. Earliest stage. Hyaline basis- (intercellular) substance, with largish 
cells (connective-tissue corpuscles); the latter drawn up in rows at regular intervals ; 
at first separated, spindle-shaped, and simple; at a later period anastomosing and 
branched. B. More advanced stage; at a, the basis-substance which has become 
striated (fibrillated), presents a fasciculated appearance on account of the cells 
imbedded in it in rows, the cells becoming narrower and smaller; at b, the striation . 
of the basis-substance has disappeared under the influence of acetic acid, and the 
fine and long anastomosing fibre-cells (connective-tissue corpuscles), still retaining 
their nuclei, are seen. | 


74. LECTURE Il. 


spindle-shaped ones, as, for example, with great regula- 
rity in the immediate neighbourhood of the articular 
surfaces. The nearer, in the 
examination of articular car- 
===—|° tilage, we approach to the 
-|, free surface (Fig. 22, a,) the 
-@{| smaller do the cells become ; 
e and, at last, nothing more is 
seen but small, flatly lenti- 

5° @). cular bodies, the substance 
9 @@ vos ‘ Ge intervening between which 
sometimes presents a slightly 
striated appearance. Here, therefore, without the tis- 
sue’s having ceased to be cartilage, a new type displays 
itself, which we much more regularly meet with in pure 
connective tissue, and hence the idea might easily arise 
that articular cartilage is invested with a special mem- 
brane. This is, however, not the case, for there is no 
synovial membrane spread over the cartilage, but its 
boundary towards the cavity of the joint is everywhere 
formed of cartilage itself. The synovial membrane only 
begins where the cartilage ceases—at the edge of the 
bone. On the other hand, we see that at certain points 
the cartilage passes directly into forms in which the cells 
become stellate, and the way is paved for their final 
anastomosis ; ultimately, spots are met with at which it 
is no longer possible to say where the one cell ends and 
the other begins, inasmuch as they communicate so 
directly one with another that it is impossible to detect 
a line of separation between their membranes. When 


Fia. 22. 














Fig. 22. Perpendicular section through the growing cartilage of a patella. a. The 
articular surface, with spindle-shaped cells (cartilage-corpuscles) disposed in layers 
parallel to it. 6. Incipient proliferation of the cells. c, Advanced proliferation ; 
large, roundish groups—within the enlarged capsules a continually increasing num- 
ber of round cells. 50 diameters. 


esate) a 


CARTILAGE—MUCOOS TISSUE. 75 


such a. case occurs, the cartilage, which up to that time 
had remained hyaline and homogeneous, becomes hete- 
rogeneous and striated, and has long since been called 
fibro-cartilage. | 

From these forms a third has been distinguished, the 
so-called reticular [yellow or spongy] cartilage, as seen 
in the ear and nose, in which the cells are round, but 
encircled by a peculiar kind of thick, stiff fibres, whose 
mode of production has not yet been thoroughly made 
out, but they are, perhaps, derived from the metamor- 
phosis of the intercellular substance. 

Under these different types, presented by cartilage in 
its different localities, all the different aspects which the 
other connective tissues offer are included. There is 
also true connective tissue with round, long, and stellate 


cells. Just in the same manner we find, for example, | 
in the peculiar tissue which I have named mucous tissue ) 
(Schleimgewebe), round cells in a hyaline, or spindle- | 
shaped ones in a striated, or reticular ones in a meshy, | 
basis-substance. The only criterion we possess for dis-— 


tinguishing them consists in the determination of the 
chemical constitution of the intercellular substance. 


Every tissue is called connective tissue whose basis- ) - 


. ¢ 


substance yields gelatine when boiled ; the intercellular 


; 
( 


/ 
; 


substance of cartilage produces chondrine ; mucous tis- » 


sue, On expression, a substance, mucin, precipitable by 
acetic acid, and insoluble in an excess of it, though dis- 
solving in muriatic acid when added in considerable 
quantity. 

Besides these, a few solitary points of difference in 
regard to peculiarity of form and contents may be pre- 
sented by individual cells at some later period of their 
existence. What we concisely designate fat is a tissue 
which is intimately connected with those of which we 
have been treating, and is distinguished from the rest by 


1 
? o 
i _/* 


76 LECTURE II. 


the fact that some of the cells enlarge and become stuffed 
full of fat, the nucleus being thereby thrust to one side. 
In itself, however, the structure of adipose tissue is pre- 
cisely the same as that of connective tissue, and, under 
certain circumstances, the fat may so completely disap- 
pear that the adipose tissue is once more reduced to the 
state of simple, gelatinous connective, or mucous tissue. 

Amongst these different species of connective tissue 
the most important for our present pathological views, 
are, generally speaking, those in which a reticular ar- 
rangement of the cells exists, or, in other words, in which 
they anastomose with one another. Wherever, namely, 
such anastomoses take place, wherever one cell is con- 
nected with another, it may with some degree of cer- 
tainty be demonstrated that these anastomoses constitute 
a peculiar system of tubes or canals which must be 
classed with the great canalicular system of the body, 
and which particularly, forming as they do a supplement 
to the blood- and lymphatic vessels, must be regarded as 
a new acquisition to our knowledge, and as in some sort 
filling up the vacancy left by the old vasa serosa which 
do not exist. This reticular arrangement is possible in 
cartilage, connective tissue, bone and mucous tissue in 
the most different parts; but in all cases those tissues 
which possess anastomoses of this description may be 
distinguished from those whose elements are isolated, by 
the greater energy with which they are capable of con- 
ducting different morbid processes. 





Li Raabe, ey be hed. 


FEBRUARY 20, 1858. 
PHYSIOLOGICAL AND PATHOLOGICAL TISSUES: 


The higher animal tissues: muscles, nerves, vessels, blood. 

Muscles—Striped and smooth—Atrophy of—The contractile substance and con- 
tractility in general—Cutis anserina and arrectores pili. 
Vessels—Capillaries—Contractile vessels—Nerves. 

Pathological tissues (Neoplasms), and their classification—Import of vascularity— 
Doctrine of specific elements—Physiological types (reproduction)—Heterology 
(heterotopy), heterochrony (heterometry), and malignity-—Hypertrophy and 
hyperplasy—Degeneration—Criteria for prognosis. 

Law of continuity—Histological substitution and equivalents—Physiological and 
pathological substitution. 


In my last lecture I portrayed to you the first two 
groups of tissues, the one embracing epithelium or epi- . 
dermis, and the other the different kinds of connective 
tissue. What still remains forms a somewhat heteroge- 
neous group, the individual members of which do not, 
indeed, in the degree that is the case with epithelium 
and connective tissue, bear a real relationship to one 
another, yet, on the whole, present a certain correspon- 
dence, in that they constitute the higher animal struc- /» 
tures, and are distinguished by their specific mode of 
development from the less highly organized epithelial 
and connective tissues. Moreover, most of them appear 
under the form of connected, more or less tubular, struc- 
tures. If a comparison be instituted between muscles, 
nerves, and vessels, the idea very readily suggests itself 

TT 


78 LECTURE III. 


that we have in all three structures to deal with real 
tubes, filled with now more, now less, moveable contents. 
But this notion, however well it may accord with a 
superficial view of the matter, does not express the 
whole truth, inasmuch as we cannot compare the con- 
tents of the different tubes. 

The blood which is contained in the vessels, cannot, 
at least at present, be regarded as analogous to the axis- 
cylinder, or the medullary [white] substance of a nerve- 
tube, or to the contractile substance of a primitive mus- 
cular fasciculus (Muskelprimitivbtindel [muscular fibre]). 
_I must, indeed, here remark, that the original develop- 
ment of all the structures which may be included in this 
group is still a subject of great controversy, and that 
the view maintaining the simply cellular structure of 
most of these elements is by no means completely estab- 
lished. This much, however, appears to be certain, that, 
at any rate in foetal parts, the blood-corpuscles are just 
as much cells as the individual constituents of the walls 
of the vessels within which the blood flows ; and that the 
vessel cannot be designated as a tube which invests the 
blood-corpuscles, as the cell-membrane does its contents. 
It is therefore necessary in the case of the vessels to 
draw a line between their contents and proper walls, 
and to repudiate the seeming resemblance between the 
vessels, and the nerves and muscular fibres. Again, if 
we wished to adopt the mode of origin of the several 
tissues as the basis of our classification, we should, in 
accordance with prevailing views, have to associate the 
lymphatic glands also with the blood, and might be 
rather reminded of a connection such as we have seen 
to exist in the relations between the epidermis and the 
rete mucosum. But here I must once more impress 
upon you that the lymphatic glands are distinguished 
from glands properly so called, not only by their not 





THE HIGHER ANIMAL TISSUES. 79 


possessing any excretory duct in the ordinary sense of 
the word, but also because from the mode of their deve- 
lopment they by no means occupy the same position 
as ordinary glands, but are on the contrary at every 
period of their existence nearly allied to the connective 
tissues, and that, therefore, the temptation would rather 
be to class them with the tissues which we see produced 
by the transformation of the connective tissues. Yet 
this would at the present moment be still rather a ven- 
turous undertaking. 

Amongst all the forms of which we have here to treat, 
the elements of muscle have generally been regarded as 
the most simple. If we examine an ordinary red muscle 
(I do not say a voluntary one, inasmuch as in the heart 
also we meet with fibres of the Fie. 98. 
same form) we find it to be essen- 
tially composed of a number of 
cylinders, for the most part of 
equal thickness (primitive fasci- 
culi [fibres]), which on a trans- 

verse section are seen to have a 
cylindrical form, and on which we 
at once perceive the well-known 
transverse striz, that is, broad cS 
lines which generally run transversely through the fasci- 
culus with a somewhat wavy outline, and are almost as 
broad as the intervals that separate them. In addition 
to this transverse striation we also see, especially when 
certain modes of preparation have been adopted, stri fol- 








Fig. 28. A group of primitive muscular fasciculi [fibres]. a. The natural appear- 
ance of a fresh primitive fasciculus, with its transverse striz (bands or discs), 6, 
A fasciculus gently acted upon by acetic acid; the nuclei stand out distinctly, and 
in one of them two nucleoli are visible, whilst in another the division is complete. 
c. A fibre acted upon more strongly by acetic acid; the contents are swollen up at 
the end, so as to protrude from the sheath (sarcolemma). d. Fatty atrophy. 300 


diameters. 


80 LECTURE III. 


lowing a longitudinal direction, and these, indeed, in 
some preparations preponderate to such a degree, that the 
muscular fasciculus appears to be striated almost exclu- 
sively in this direction. If now we add acetic acid, there 
are forthwith disclosed immediately beneath the sheath, 
and now and then also more towards the centre, nuclei 
which are tolerably large, and mostly contain large nucle- 
oliin greater or less number. In this manner, therefore, 
after we have cleared up the internal substance by the 
application of acetic acid, we again obtain an appearance 
which reminds us of the original cell-form ; and there 
has been the greater tendency to regard the whole of a 
primitive fasciculus as having sprung from a single cell, 
because. according to the view which was formerly 
entertained, the individual primitive fasciculi of every 
muscle were thought to extend from the point of origin 
to that of insertion, and were therefore held to be 
as long as the muscle itself. This latter supposition 
has, however, been shaken by investigations which 
were set on foot in Vienna, under Briicke’s direction 
by Rollet, for he demonstrated that in the course of 
muscles the ends of primitive fasciculi are to be seen 
running into points, so that a primitive muscular fasci- 
culus would comport itself lke a large fibre-cell (Fig. 
105, A). These ends fit one into the other, and, accord- 
ing to this, the length of a primitive fasciculus would by 
no means correspond to the whole extent of the muscle. 

On the other hand, I must remark, that observations 
have been made in different quarters quite recently, 
which are rather of a nature to throw doubts upon the 
uni-cellular nature of these elements. Leydig regards 
them as rather containing a series of cells of a smaller 
kind, between which the contractile substance is lodged, 
his idea being based upon the circumstance that every 
nucleus (Figs. 23, 6, c; 24, B) is enclosed in a special 








TRANSVERSELY STRIATED MUSCLES. 81 


elongated cavity.’ In discussions respecting these ulti- 
mate elements of muscle, extremely difficult relations 
are involved, and I for my own part must confess that, 
however much I am inclined to admit the uni-cellular 
nature of the primitive fasciculi, I am still too familiar 
with the peculiar appearances in their interior not to be 
obliged to allow that another 
view may beadvanced. For 
the present, however, we 
must bear in mind that we “aN 

have to do with a structure a \\e 
in which an external mem- 
branous sheath (sarcolem- 
ma) and contents are to be 
distinguished. In the latter, acetic acid causes nuclei 
to show themselves, and, when they (the contents) are 
in their natural condition, the peculiar transverse and 
longitudinal striation may be recognised in them. This 


Fig. 24. 





Fig. 24. Muscular elements from the heart of a puerperal woman. A. Peculiar 
spindle-shaped cells precisely like the fibre-cells of the pulp of the spleen, probably 
belonging to the sarcolemma and set free in teasing out the preparation. a, Cres- 
centically curved cell, somewhat flat at one end, viewed on its surface. 6. A 
similar one, seen in profile, with flat nucleus. c¢, d.' Cells, the nuclei of which lie 
in a hernial protrusion of the membrane. e. A similar cell, viewed on its sur- 
face, with its nucleus, as it were, lying upon it. 2B. A primitive fasciculus, without 
its sheath (sarcolemma), with distinct longitudinal fibrils and large, roundish nuclei, 
of which one contains two nucleoli (incipient partition). C. A primitive fasciculus, 
which has been teased asunder and slightly cleared up by acetic acid; besides a 
divided nucleus, fine, awl-shaped, nucleus-like bodies are seen imbedded between 
the longitudinal fibrils. 300 diameters. 


1 This cavity Leydig supposes to be lined by a membrane, and therefore really 
to constitute a cell (connective-tissue corpuscle). The nuclei of every primitive 
fasciculus would, therefore, according to this view, be the nuclei of connective- 
tissue corpuscles, and the contractile substance, lying between these, would be 
equivalent to the intercellular substance of ordinary connective tissue. The nuclei 
here alluded to are the ordinary nuclei of muscle, as seen in the figs. quoted above 
and must not be confounded with the awl-shaped bodies represented in fig. 24, C, 
‘lying between the fibrils; for, though these bodies look like nuclei, they are really, 
according to Leydig, portions of the divided processes of some of his connective- 
tissue corpuscles.— From a MS. note by the Author. 

6 


89 : LECTURE III. 


striation is altogether internal and not external. The 
membrane in itself is perfectly smooth and even; the 
transverse striation belongs to the contents, which, when 
seen in a mass, form the red substance of the muscle. 
Now it is this substance which has the property of 
contractility indubitably inherent in it, and even varies 
in appearance according to its state of contraction, be- 
coming broader when contracted, whilst the intervals 
between the individual transverse bands become some- 
what narrower, so that a change in the arrangement of 
its minutest constituents takes place, and this, as seems 
probable from the investigations of Briicke, not merely ° 
in the case of its physical molecules, but also in that of 
its visible anatomical constituents. Briicke, namely, 
by examining muscle by polarized light, has discovered 
different optical properties in the individual layers of 
substance—in those which compose the transverse strize 
and those which form the intervening mass. On the 
adoption of certain methods of preparation, every pri- 
mitive muscular fasciculus appears to be made up of 
plates or discs of a different nature, piled up one above 
another, and these in their turn to be entirely composed 
of minute granules (Bowman’s sarcous elements). In 
reality, however, the contents of a primitive fasciculus 
consist of a certain number of fine, longitudinal fibrils, 
every one of which contains minute granules correspond- 
ing in position to the transverse strie or apparent discs 
of the primitive fasciculus, and held together by a pale, 
intervening substance. Now, since a considerable num- 
ber of primitive fibrils le in apposition side by side, 
there arises, in consequence of the symmetrical position 
of the little granules, this very appearance of discs which 
really do not exist. In proportion to the activity of the 
muscle these parts assume an altered position with re- 
gard to one another ; during contraction the granules 

















SMOOTH MUSCLES. 88 


are approximated, whilst the intervening substance be- 
comes shorter and, at the same time, broader. 
Compared with this, the structure of the smooth, or- 
ganic, or, although this is a less expressive term, invo- 
luntary muscular fibres, appears much more simple. On 
examining any part of those organs in which smooth 
muscular fibres are contained, we find in the majority of 
cases, first of all, just as was the case with the transversely 
striated muscles, little fasciculi—as, for example, in the 
muscular coat of the urinary bladder. Within these 
fasciculi, upon further investigation, a series of distinct 
elements can be distinguished, of which a certain num- 
ber, six, ten, twenty, or more, are held together by a 
common connective substance. According to the notion 
which universally prevailed a. oe 
until quite recently, every 
one of these elements was 
analogous to the primitive 
fasciculus of striped muscle. { 
For as soon as we succeed | 
in separating these fascicull 
of smooth muscle into their \ 
more minute constituents, 
we find their ultimate ele- 
ments to consist of long, 
spindle-shaped cells, which 
usually contain a nucleus in 
their centre (Fig. 5, 2). According to the view on the 
contrary, which, especially in consequence of the impul- 
sion given by Leydig’s investigations, has quite lately 





Fig. 25. Smooth muscular fibres from the parietes of the urinary bladder. A. 
Fasciculus still coherent, out of which at a, a single isolated fibre-cells protrude, 
whilst at 6 their simple divided ends appear. B. A similar fasciculus after being 
treated with acetic acid, whereby the long and narrow nuclei have become evident. 
a, and 6, as above. 300 diameters. 


84. LECTURE III. 


begun to be mooted in various quarters, we should have 
to regard the bundle, in which a whole series of fibre- 
cells is contained, rather as analogous to a transversely 
striated primitive fasciculus. Until, however, this point 
has been satisfactorily settled, I consider it advisable and 
more in accordance with known facts to regard each 
fibre-cell as the equivalent of a primitive fasciculus. 
Should, however, any change of opinion shortly occur, 
you will now at any rate be prepared for it. 

In one of these spindle-shaped or fibre-cells it is diffi- 
cult to distinguish anything particular. In very large 
cells of this kind, and with a high magnifying power, we 
can certainly frequently distinguish a fine longitudinal 
striation (Fig. 5, 5), so that it looks as if here, too, fibrils 
of some sort were disposed lengthways in the interior, 
whilst ordinarily no trace of any transverse strise is per- 
ceptible. Yet the pale, smooth muscles exhibit, chemi- 
cally speaking, a pretty close agreement with the trans- 


_versely striped ones, since a similar substance (the 


so-called Syntonian of Lehmann) can, by the help of di- 
luted hydrochloric acid, be extracted from both; and 
one of the most characteristic substances which is met 
with in red muscles, namely Creatine, is met with also, 
according to the investigations of G. Siegmund, 1 in the 
smooth muscular fibres of the uterus. 

One of the preparations of red muscle which I have 
placed before you exhibits an appearance which is also 
pathologically interesting ; among the fasciculi, namely, 
is one which presents the condition of the so-called pro- 
gressive (fatty) atrophy. The degenerated fasciculus is 
smaller and narrower, and at the same time little 
fat-globules are seen arranged in rows between the lon- 
gitudinal fibrils (Fig 238, d). Atrophy in muscles is 
chiefly characterized by gq diminution in the diameter of 
the primitive fasciculi affected; in fatty atrophy the 


CONTRACTILITY. 85 


more palpable change is added, that little rows of fat- 
globules appear in the interior of the primitive fascicu- 
lus, during the accumulation of which the proper con- 


tractile substance decreases in bulk. The more fat there . 


is, the less contractile substance ; or, in other words, 
the muscle becomes less capable of performing its func- 
tions in proportion as the normal contents of its fibres 
diminish. Pathological experience, therefore, also de- 
signates as the seat of the contractile power a definite 
substance, the occurrence of which, as especially the im- 
portant investigations of Kélliker have taught us, is con- 
nected with certain histological elements. Whilst for- 
merly many other things besides the substance of muscle, 
as for example, certain forms of connective tissue, were 
assumed to be contractile, lately the whole theory of 
contractility in the human body has been withdrawn 
within the limits of that substance, and observers have 
succeeded in tracing back nearly all the peculiar pheno- 
mena of motion to the existence of minute parts of a 
really muscular nature. Thus, in the human skin there 
lie little muscles about as large as the smallest fasciculi 
in the parietes of the urinarybladder, bundles consisting 
of diminutive fibre-cells, which run from the base of the 
hair-follicles towards the surface of the skin, and, when 
they contract, approximate the two. The result of this 
is naturally that the skin becomes uneven, and we get 
what is called a goose-skin. This singular phenomenon, 
which was previously regarded as inexplicable, has been 
simply explained by the demonstration of these purely 
microscopical muscles, the arrectores pilorum. 

So also we now know that the greater part of the 


muscular layers in vessels is composed of elements of 4, 
this kind, and that the phenomena of contraction exhi- - 


bited by the vessels must be referred solely and exclu- 
sively to the action of muscular fibres, which are con- 


) 


i 


86 . LECTURE III. 


tained in them in the form of circular or longitudinal 
layers. A small vein or a small artery can contract only 
in proportion to the quantity of muscle with which it is 
provided, and they are only distinguished by the circum- 
stance that either the longitudinal or the transverse mus- 
cular layers are the more strongly developed. 

I have called your attention to this point because you 





can see from it, how a simple anatomical discovery may 
supply the most important information with regard to 


Fig. 26. Small artery from the base of the cerebrum after the application of acetic 
acid. .A. Small trunk; B and C, larger branches; D and Z, branches of the 
smallest size (capillary arteries). a, a. External coat, with nuclei, which run in the 
direction of the length of the vessel, and are seen first in a double and afterwards 
in a single layer, with a striated basis-substance ; at D and # the coat is reduced 
to a single layer, with longitudinal nuclei, which here and there have been replaced 
by masses of fat-granules (fatty degeneration). 6, 6. Middle coat (circular fibrous, 
or muscular, coat), with long, cylindrical nuclei, which run transversely around the 
vessel, and at.its borders (where they look as though they had been cut across) 
present the appearance of round bodies; at D and # transverse nuclei of the middle 
coat becoming continually scarcer. c, ¢. Internal coat, at D and # with longitudi- 
nal nuclei. 300 diameters. 


VESSELS. , 87 


physiological facts, which are widely separated from one 
another, and how the demonstration of definite morpho- 
logical elements may at once most essentially contribute 
to the elucidation of functions, which, without any such 
data, would be utterly incomprehensible. 

I will omit to speak here of the more intimate struc- 
ture of the nervous system, because I shall have occasion 
hereafter to consider it in a more connected form, else 
this would be the subject which would most suitably 
come next, seeing that there exist many points of resem- 
blance in the structure of muscular and nerve-fibres. 
But in the nervous system we find, in addition, nerve- 
cells (Ganglienzellen), which connect the individual fibres 
with one another, and must be regarded as the most 
important storehouses for all nervous energy. 


Concerning the structure of the vascular system also I | 


will not here treat in detail, but will only say as much 
as is necessary to give a cursory view of the matter. 

A. capillary vessel is a simple tube (Fig. 3, c), in which 
we have, with the aid of our present appliances, hitherto 
only been able to discover a simple membrane, beset at 
intervals with flattened nuclei, which, when seen in the 
middle of the surface of the vessel, present the same ap- 
pearance as in the elements of. muscle, only that they usu- 
ally lie more at the sides, and therefore frequently have 
an awl-shaped appearance, from their sharp border alone 
being perceived. It is this, the most simple class of 
vessels, which we now-a-days solely and exclusively cali 
capillaries, and with regard to them we cannot say that 
they become wider or narrower by means of any action 
of their own, but at most that their elasticity renders a 
certain degree of contraction possible. Nowhere are 
there to be witnessed in them genuine processes of con- 
traction or relaxation succeeding it. The discussions 
which formerly took place with regard to the contracti- 


H 
{ 


88 LECTURE III. 


lity of the capillaries really had reference to small arte- 
ries and veins, the calibre of which grows narrower 
through the contraction of their muscular coats, or wider 
upon the occurrence of relaxation in consequence of the 
pressure of the blood. This is one of the first facts, and 
an important one it is, which have resulted from the 
more accurate histological knowledge of the smaller and 
larger vessels, and it shows us that we cannot speak of 
the general properties of vessels, inasmuch as the capil- 
laries differ essentially in structure from the small arte- 
ries and veins. These are composite structures, partak- 
ing of the nature of organs, whilst a capillary vessel is 
rather a simple histological element. 

Now that we have, gentlemen, completed a very 
general survey of the physiological tissues, the question 


arises, how the pathological ones in their turn comport 
themselves. By pathological tissues, of course, those 


only can be meant which really constitute pathological 
new formations, and not physiological parts which have 
simply undergone alteration in consequence of some 
deviation from the normal processes of nutrition. We 
have in them to deal with genuine neoplasms, with the 
additional matter furnished by the growth of new tissues 
in the course of pathological processes, and the question 
is, whether the general types which we have established 
for the physiological tissues will also be found to hold 
good in the case of the pathological ones. To this I un- 
reservedly reply, yes ; and however much [ herein differ 
from many of my living contemporaries, however posi- 
tively the peculiar (specific) nature of many pathological 
tissues has been insisted upon during the last few years, 
I will nevertheless endeavour in the course of these lec- 
tures to furnish you with proofs that every pathological 
structure has a physiological prototype, and that no 
form of morbid growth arises which cannot in its ele- 





CLASSIFICATION OF NEOPLASMS. 89 


ments be traced back to some model which had pre- 
viously maintained an independent existence in the 
economy. 

The classification of pathological new formations, of 
genuine neoplasms, was formerly by most observers 


attempted to be based upon their different degrees of /p, 2 fe 


vascularity. If you examine the different treatises which 
appeared upon this subject up to the time of the cell- 
theory, you will find that the question of organization 
was always decided by that of vascularity. Every part 
which contained vessels was regarded as organized, and 
every part as unorganized which was destitute of ves- 
sels. But this, according to present notions, is an 
incorrect view of the matter, inasmuch as we have also 
physiological tissues without vessels, as for example, 
cartilage. 

But at a time when the more minute elements of 
tissues were at most only known as globules, and when 
very different virtues were attributed to these globules, 
it was quite excusable that everything should be referred 
to the vessels, particularly after the comparison John 
Hunter made between pathological new formations and 
the development of the chick in the egg, when he endea- 
voured to show that, just as the punctum saliens in the 
hen’s egg constitutes the first phenomenon of life, the 
vessels also where the first things to:show themselves in 
pathological formations. You no doubt still remember 
how several ‘‘ parasitical” new formations were de- 
scribed by Rust and Kluge as provided with an inde- 
pendent vascular system, which without having any 
connection with the old vessels, developed itself quite 
independently, as is the case in the chick. Many 
attempts had indeed been made even before this to 
refer the apparently so irregular forms of néw formations 

to physiological paradigms, and herein essential service 


90 LECTURE III. 


has been rendered by natural philosophers. At the time 
when theromorphism played a conspicuous part, and 
many analogies were discovered between pathological 
processes and the normal states of inferior animals, com- 
parisons also began to be instituted between new for- 
mations and familiar parts of the body. Thus, Johann 
Friedr. Meckel, the younger, spoke of mammary and 
pancreatic sarcoma. What has very recently been 
described in Paris as heteradenia (Heteradenie), or a 
heterologous formation of glandular substance, was in 
the school of the natural Se oa a pretty generally 
accepted fact. 

Since the study of embryology has been prosecuted in 
a more histological manner, the conviction has gradually 


' more and more been acquired, that most new formations 


contain parts which correspond to some physiological 
tissue, and in the micrographical schools of the west a 
certain number of observers have come to the conclusion, 
that in the whole series of new formations there is only 
one particular structure which is specifically different 
from natural formations, namely cancer. With regard 
to this, the most important points urged are, that it 
differs altogether from every other tissue, and that it 
contains elements sua generis, whilst, singularly enough, 
a second formation, between which and cancerous tissue 
the older writers were wont to draw parallels, namely 
tubercle, has—although to it too nothing strictly analo- 
gous could be discovered—been much neglected, owing 
to its having been regarded as an incomplete and some- 
what crude product, and as a structure which had never 
become properly organized. Yet, upon a more careful 
examination of cancer or tubercle, we shall find that 
everything depends upon our searching for that stage in 
their development, in which they are exhibited in their 
perfect form. We must not examine at too early a 


CLASSIFICATION OF NEOPLASMS. 91 


period, when their development is incomplete, nor yet 
at too late a one, when it has proceeded beyond its 
highest point. If we restrict our observations to the 
time when development is really at its height, a phy- 
siological type may be found for every pathological 
formation, and it is just as possible to discover such 
types for the elements of cancer as to find them, for 
example, for pus, which, if it be sought to maintain the 
specific nature of certain formations, is just as much 
entitled to be regarded as something peculiar as cancer. 
Both of them stand upon precisely the same footing in 
- this respect, and when the older writers spoke of cancer- 
pus they were in a certain measure right, inasmuch as 
cancer-juice is only distinguished from pus by the higher 
degree of development to which its individual elements 
have attained. | 

A classification of pathological structures also may be 
made upon exactly the same plan as that which we have 


already ventured upon in the case of the physiological . 
tissues. In the first place, there are also among these - 


structures some which, like the epithelial ones, are essen- 
tially composed of cellular elements, without the addition 
of anything else of consequence. In the second place, 
we meet with tissues which are allied to those called 
connective, inasmuch as in addition to the cells a certain 


quantity of intercellular substance is present. In the 


third and last place come those formations which are 
akin to the more highly organized structures, blood, 
muscles, nerves, etc. Now, a point to which I must at 
once direct your attention is, that in pathological forma- 
tions those elements the more frequently exist, and the 
more decidedly prevail, which do not represent the 
higher grades of really animal development, and that, 
therefore, on the whole, those elements are most rarely 
imitated which belong to the more highly organized, and 


iba Ad 


92 LECTURE III. 


especially, to the muscular and nervous, systems. Still, 
these formations are by no means excluded; we find 
pathological new formations of every description, no 
matter to what tissue they may be analogous, provided it 
possesses distinctive features. It is only with regard to 
their frequency and importance that a difference prevails, 
and this is of such a nature that the great majority of 
pathological productions contain cells analogous to epi- 
thelial cells, or to the corpuscles of the connective 
tissues, and that of those structures which we have 
included in the last class of normal tissues, the vessels 
and parts which may be compared with lymph and 
lymphatic glands are the most frequently met with as. 
new formations, whilst real blood, muscles, and nerves, 
are the most seldom found as such. 

But, if we ultimately arrive at such a simple view of 
the matter, the question of course arises, what becomes 
of the doctrine of the heterology of morbid products, to 
the upholding of which we have long been accustomed, 
and to which the most simple reflection almost inevita- 
bly conducts us. Hereunto I can return no other an- 
swer than that there is no other kind of heterology in 
morbid structures than the abnormal manner in which 
they arise, and that this abnormity consists either in the 
production of a structure at a point where it has no 
business, or at a time when it ought not to be produced, 
or to an extent which is at variance with the typical 
formation of the body. So then, to speak with greater 

precision, there is either a Heterotopia, an aberratio loci, 
or an aberratio temporis, a Heterochronia, or lastly, a 
mere variation in quantity, Heterometria. But we must 
be very careful not to connect this kind of heterology in 
the more extended sense of the word with the notion 
of malgnty. Heterology is a term that, in its histolo- 
gical meaning may be applied to a large proportion of 


ac / 


| HYPERTROPHY AND HYPERPLASY. 93 


pathological new formations, which, as far as the prog- 
nosis is concerned, may unquestionably be called benig- 
nant ; itis not rare for a new formation to occur at a 
point where it is certainly entirely misplaced, but at the 


_ same time does not occasion any considerable mischief. 


A lump of fat may very likely arise in a place where we 
should expect no fat, as, for example, in the submucous 
tissue of the small intestines, but, let the worst come to 
the worst, the result is only a polypus, which protrudes 
on the inner surface of the bowel, and may become 
tolerably large without giving rise to any symptoms of 
disease. 

If we consider the structures which are called 


ae pe ov Iheterologous in the more restricted sense of the word, ,. , 


, with reference, namely, to the points at which they)! — 


arise, they may be easily separated from the homo-.. 


logous ones (homeeoplastic ones of Lobstein), by their... 


deviating from the type of the part in which they arise. i: 


When a fatty tumour arises in fatty tissue, or a connec- 
tive tissue (fibrous) tumour! Bindegewebs-Geschwulst) in 
connective tissue, the type followed in the formation of 
the new structure is homologous to the type followed in 
the formation of the old one. All such formations are, 
as usually designated, included under the term hyper- 
trophy, or under that of hyperplasia, if we adopt the 


name I have proposed for the sake of more accurate dis-~”, 
tinction. Hypertrophy, according to the meaning which ° 


I attach to the word, designates those cases in which the 
individual elements 4f a structure take up a considerable 
amount of matter, and thereby become larger; and in 
consequence of the simultaneous enlargement of a num- 
ber of elements, at last the whole of an organ may. be- 
come swollen. When a muscle becomes thicker, all its 
primitive fasciculi become thicker. A liver may become 


hypertrophied simply in consequence of a considerable 


94 LECTURE III. 


enlargement of its individual cells. In this case there 
is real hypertrophy without, properly speaking, any 





new formation. ssentially different from this process 
are the cases in which an enlargement takes place in 
consequence of an zncrease in the number of the elements. 
A liver, namely, may also become enlarged by a very 
abundant development of a series of small cells in the 
place of the ordinary ones. Thus, when simply hyper- 
trophied, we see the panniculus adiposus of the skin swell 
up in consequence of every single fat-cell’s absorbing a 
larger quantity of fat than usual, and when this takes 
place in thousands upon thousands, nay, we may say, 
in hundreds of thousands and millions of cells, the re- 
sult is very obvious and strikes the eye (polysarcia). 
but it is just as possible for new cells to form in addi- 
tion to the old ones, and for an increase of size to take 
place without any enlargement of the individual cells. 


Fig. 27. Diagrams of hepatic cells. .A. Their simple physiological appearance. 
B. Hypertrophy: a, simple; 6, with accumulation of fat (fatty degeneration, fatty 
liver). C@. Hyperplasy (numerical or adjunctive hypertrophy). a. Cell with nucleus 
and divided nucleolus. 4% Divided nuclei. ¢, ce. Divided cells. 





DEGENERATIVE NEW FORMATIONS. 95 


These are essentially different processes, and may be 
styled semple and numerical hypertrophy. 

Hyperplastic processes (numerical hypertrophy) in all 
cases produce a tissue similar to that of the original 


part ; hyperplasia of the liver gives rise to new hepatic lu: 


cells ; that of a nerve to new nerve-substance ; that of 
the skin to a fresh production of the elements of the 
skin. A heteroplastic process, on the contrary, engen- 
ders histological elements which correspond, indeed, to 
natural forms, elements, for example, resembling in 
structure those peculiar to glands, nerve-substance, the 
connective and epithelial tissues, but these elements do 


not arise in consequence of a ‘simple increase in the |” 
number of such as previously existed, but in conse- |. ™~ 
quence of a change in the original type of the parent || 


tissue. When cerebral matter forms in the ovary, it 
does not arise out of pre-existing cerebral matter, nor 
through any act of simple cell-proliferation ; when epi- 


dermis springs up in the muscular substance of the | 


heart, however much it may correspond to that on the 
external surface of the skin, it is, notwithstanding, a 
heteroplastic structure. When we find hairs quite natu- 
ral in structure in the substance of the brain, however 
great the correspondence they exhibit with the hairs of 
the external surface, they will nevertheless be hetero- 
plastic hairs. In like manner we see cartilaginous tis- 
sue arise, without the existence of any essential differ- 
ence between it and ordinary, familiar cartilage, as, for 


example, an enchondromata. Still, an enchondroma is — 


a heteroplastic tumour, even when occurring in bone, 
for perfect bone has no longer any cartilage in the parts 
where the enchondroma forms, and the term cartidage of 
bone (Knochenknorpel), as a designation for the organic 
basis of bone, is nothing but aterm. It is either from 
osseous or medullary tissue that the enchondroma 


96 LECTURE III. 


springs, and at the very point where real cartilage ex- 


c\ ists, for example, at the articular ends of the bone, no 
/ ‘cartilaginous tumours, in the ordinary sense of the word, 


arise. It is not, therefore, with an hypertrophy of pre- 


i. existing cartilage that we have here to deal, but with a 
(..e*genuine new formation, which begins with a change in 


the local histological type. According to this manner 


Se of viewing the subject which is essentially different from 


that previously current, no attention is therefore paid, 
in considering the question of the heterologous nature of 
a new formation, to the composition of the structure as 
such, but only to the relations which subsist between it 
and the parent soil from which it springs. Heterology, 
in this sense, designates the difference of development 
in the new, as contrasted with the old, tissue, or, as we 


( are wont to say, a degeneration, a deviation from the 
~ typical conformation. 


This is, as you will see, also really he most important 
point upon which we can ground our prognosis. We 
find tumours, which present the most striking resem- 
blance to the most familiar physiological tissues. An 
epidermic [epithelial] tumour (Hpidermis-Geschwulst) 
may, as I have already pointed out, in its elementary 
structure entirely correspond to ordinary epidermis, but 


in spite of this it-is not always a benignant tumour of 


merely local import, which may be traced to a merely 
hyperplastic increase in pre-existing tissues, for it some- 
times arises in the midst of parts which are far from 
containing epidermis or epithelium, as, for example, in 
the interior of lymphatic glands, or in that of thick 
layers of connective tissue, which are at a distance from 
any surface, and even in bone. In these cases the for- 
mation of epidermis is certainly quite as heterologous as 
it is possible to conceive anything to be. But practical 
experience has shown us that it was altogether incorrect 








REPRODUCTION OF PHYSIOLOGICAL TISSUES. 97 


to conclude from the mere correspondence of the patho-/ f>"7;* 
logical tissue with a physiological one, that the case would ° tof 
continue to follow a benignant course. Ki at 


It has been, as I must remark with particular empha- 
sis, one of the greatest, and at the same time best-founded, 
reproaches which have been levelled against the most 
recent micrographical doctrines, that, regarding the sub- 
ject from the certainly excusable point of view, namely, 
the correspondence between many normal and abnormal 
structures, they have declared every pathological new 
formation to be innocuous which exhibits a reproduction | 
of pre-existing and familiar tissues of the body. If what 
I have communicated to you as my view be correct, 
namely, that throughout the whole range of pathological 
growths no structure of an absolutely new form is to be 
found, but that we everywhere meet with structures 
which may in one way or anotber be regarded as the 
reproduction of physiological tissues, then this point of 
view falls to the ground. In support of my view, I can 
at least adduce the fact that I have, in all disputes con- 
cerning the innocent or malignant nature of definite | _ 
forms of tumours, up to the present time always proved pairs 
to be in the right. 

Before we quit the consideration of General Histology, 

I would invite your attention for a few moments to a 
few points of primary importance which obtrude them- 
selves upon us on nearly every occasion. Whilst, namely, 
the animal tissues were being studied in their affinities 
to one another, questions relating to these affinities were 
at different times stumbled upon, which gave rise to 
generalizations that were more of a physiological cha- 
racter. 

When Reichert undertook to collect the connective 
tissues into one larger group, he set out with this position 


chiefly, that the demonstration of the continuity of ts- 
T 


Si yt ne ae >" 


98 LECTURE III. 


sues must be regarded as a decisive proof of their inti- 
mate relationship. That as soon as one part could 
be made out to be continuously (by union, not mere 
juxtaposition) connected with another, both must be 
regarded as parts of a common whole. In this manner he 
sought to prove that cartilage, periosteum, bone, tendons, 
fasciee, etc., really formed a continuous mass, a kind of 
basis-tissue (Grundgewebe) for the body, a connective sub- 
stance, which had only experienced certain changes in 
these different localities, without their being, however, 
of such a nature as to destroy the character of the tis- 
sue as such. This so-called daw of continuity soon suf- 
fered the most violent shocks, and quite recently such a 
terrible breach has been made in it, that it can scarcely 
any longer be possible to derive therefrom any general 
criterion for the determination of the nature of a tissue. 
On the other hand, namely, new facts have been con- 
tinually brought forward in support of the continuity ot 
such histological elements as, according to Reichert, would 
be separated ¢oto ce/o from one another, as, for example, 
of epithelial and connective tissue ; and there has been 
a continually increasing mass of evidence in support of 
the assertion that cylindrical epithelium is capable of 
becoming elongated into fibres, which in the shape of 
filaments anastomose with connective-tissue corpuscles. 
Nay, it has been quite recently asserted by a whole 
series of observers that these superficial cells are pro- 
longed inwardly, and then enter into direct connection 
with nerve-fibres. With regard to this last point, I 
must confess that I am not yet convinced of the correct- 
ness of the representation ; but with respect to the for- 
mer one, that is a matter which will probably end in the 
demonstration of the real continuity of the elements. 
It would seem, therefore, that it is even now no longer 
possible to mark out the exact limits which divide every 





| 

















HISTOLOGICAL EQUIVALENTS AND SUBSTITUTIONS. ~ 99 


kind of epithelium from every kind of connective tissue, 
but only where scaly epithelium is met with, whilst the 
limits are doubtful wherever cylindrical epithelium exists. 
Just in the same manner elsewhere also do the bound- 
ary lines become obliterated. Whilst formerly the lim- 
its which separate the elements of muscle from those of 
tendon were considered to be most distinctly defined, 
extremely decisive proofs have in this case also been 
afforded, and first by Hyde Salter and Huxley, that fibres 
proceed from connective-tissue corpuscles, which whilst 
ursuing their course in an inward direction, all at once 
assume the character of transversely striped muscle. So, 
then, in the case of connective tissue, it would seem 
there exists a continuous connection between the ele- 
ments of the surface and the more highly developed ones 
of the deeper parts. Now if, on the other hand, it has 
turned out to be very probable that the corpuscles of 
connective tissue have definite relations to the vascular 
system, we are, as you see, almost justified in regarding 
this tissue as a kind of neutral ground for parts to meet 
upon (indifferenter Samelpunkt), as a peculiar arrange- 
ment for their intimate connection, an arrangement 
which, though certainly not exercising any great influence 
upon the higher functions of the animal, is yet of great 
importance as far as its nutrition is concerned. 
In the place of the law of continuity, therefore, we 
must necessarily put something else. And here, I think, 


the doctrine which has the strongset claims to our atten- | 


tion is that of histological substitution. In the case of 


all tissues of a like nature it is quite possible, even — 
whilst confining our attention to what occurs physiologi- _ 


cally in the various classes of animals. to find one tissue 


at a certain fixed point of the body replaced by an analo- | 
gous one belonging to the same group, or, in other 


words, by an histological equivalent. 


A spot invested with cylindrical, may acquire scaly, 


) 


FANE 


100 LECTURE III. 


epithelium. A surface upon which cilia were originally 
seen, may afterwards be found to have ordinary epithe- 
lium. Thus, on the surface of the ventricles of the brain 
we meet at first with ciliated, and at a later period with 
simple scaly, epithelium. Thus, too, we see the mucous 
membrane of the uterus usually covered with ciliated — 
epithelium, but during pregnancy we find the layer of 
ciliated cylinders replaced by one of squamous epithe- 
lium. Thus, also, in places where soft epithelium ordi- 
narily is found, epidermis may, under particular circum- 
stances, be generated, as, for example, in the prolapsed 
vagina. Thus, again, in the sclerotic coat of the eyes 
of fish, cartilage is found, whilst in man this tunic con- 
sists of dense connective tissue ; in many animals bone 
is found in parts of the skin, where in man there is only 
connective tissue; but in man, too, in many places 
where there was original cartilage, osseous tissue is 
afterwards discovered. But the most striking instances 
of such substitutions are met with in muscles. One 
animal has transversely striped muscular fibres in the 
same place that another has smooth ones. 

In diseased conditions pathological substitutions occur, 
in which a given tissue is replaced by another ; but even 
when this new tissue is produced from the previously 
existing one, the new formation may deviate more or 
less from the original type. There is therefore a great 
chasm between physiological and pathological substitu- 
tion, or at least, between the physiological and certain 
forms of the pathological one. 

Physiologically, the substitution is constantly effected 
by the introduction of another tissue of the same group 
(homology) ; pathologically, very frequently by the 
agency of a tissue belonging to another (heterology). To 
this we must reduce the whole doctrine of the specific 
elements of pathology which have played so conspicuous 
a part in the last twenty years. 





Ge TU BR BV. 


FEBRUARY 24, 1858. 
NUTRITION AND ITS CHANNELS. 


Action of the vessels—Relations between vessels and tissues—Liver—Brain—Mus- 
cular coat of the stomach—Cartilage—Bone. 

Dependence of tissues upon vessels—Metastases—Vascular territories [Gefissterri- 
torien] (vascular unities)—Conveyance of nutriment in the juice-conveying 
canals (Saftkandle) of the tissues—Bone—Teeth—Fibro-cartilage—Cornea— 
Semilunar cartilages. 


AccorpiInG to the ideas usually entertained with re- 
gard to nutrition, the vessels are regarded as the canals 
by means of which not only the interchange of material 
(Stoffverkehr) is accomplished, but upon the assistance 
of which, sometimes actively and sometimes passively 
afforded, reliance is placed whenever it is required 
to control an individual part in its interchange of 
material. The regulating principle in the process of 
nutrition was long designated by an expression which 
has even crept into the language of the present day, 
namely, the ‘‘ action of the vessels,” as if they were 
endowed with a special power of actively influencing the 
condition of the neighbouring histological constituents. 

As I pointed out to you the last time, when upon the 
subject of muscular fibres (p. 85), we can now-a-days 
only speak of action in the vessels as far as muscular 


fibres are present in them, and the vessels are thus 
101 


102 LECTURE IV. 


enabled by the contraction of these fibres to grow narrower 
or shorter. This narrowing of their channel may have 
the effect of impeding transudation of fluids, whilst, on 
the contrary, in the case of the relaxation or paralysis of 
the muscular fibres, the widening of the vessel may 
favour such transudation. Let us admit this for the pre- 
sent, but allow me, before proceeding farther, to enter 
somewhat into the analysis of the mass of tissue which 
lies around the vessels, and is generally conceived to be 
of a very simple and uncomplicated nature. 

If we select parts where the vessels lie very closely 
packed, and there is perhaps nearly as much vessel as 
tissue, as, for example, the /iver, in which this condition 
really does occur (for a liver, when its vessels are full, 
contains nearly as large a volume of vessels as it does of 
proper hepatic substance), we see that the interstices 
which are left between the vessels are filled with quite a 
small number of cells. 

If we examine a single acinus of the liver by itself, 
we find, when a very lucky transverse section has been 
obtained, in its centre the eee 
vena centralis or intralobula- ), 
ris, which runs into the hepa- f 
tic vein, at the periphery 
branches of the portal vein, 
which send capillary twigs in- f 
to the interior. These at gy 
once form a network, which f , 
at first has long, but after- 
wards more regularly shaped, meshes, and extends in 
the direction of the central (or hepatic) vein, and at last 
terminates in it. The blood, therefore, after it has en- 





Fig. 28. Section from the periphery of the liver of a rabbit; the vessels com- 
pletely injected. 11 diameters. 


CAPILLARY VESSELS OF THE LIVER. 103 


tered by the interlobular (or portal) vein, flows through 
the capillary network into the intralobular vein, whence, . 
by means of the hepatic veins, it is conducted back again 
to the heart. Now, in the case of an injected liver, this 
network is seen to be so close that what interstices there 
are left seem almost to occupy less room than the ves- 
sels themselves. We can thus easily imagine how the 
older anatomists, such as Ruysch, came to be led by 
their injections to the supposition that nearly everything 
in the body was made up of vessels, and that the differ- 
ent organs were only distinguished by differences in the 
arrangement of their vessels. But just the opposite to 
what is observed in an injected preparation does the 
proportion between vessel and tissue appear to be in an 
ordinary specimen from a liver. In this the vessels are 
scarcely perceptible. A similar network is indeed seen, 
but it is the network formed by the hepatic-cells (Fig. 
27), which, closely crowded, one against the other, fill 
up all the inter-spaces of the vessels. It is plain, there- 
fore, that the capillary and hepatic-cell networks are 
interwoven in the most intricate manner, so that cells 
belonging to the parenchyma of the liver everywhere lie in 
almost immediate contact with the walls of the vessels, 
there being at most a fine layer between the cells and 
the walls, concerning which it is still a matter of dispute 
amongst histologists whether it is to be regarded as a 
peculiar coat, constituting the finest gall-ducts, or only 
as a very small quantity of connective tissue accom- 
panying the vessels. 

In this extremely simple case, a tolerably simple rela- 
tion may certainly be assumed to exist between the ves- 
sels and the cells ; it may be conceived that the blood 
which flows through the vessels may, in proportion to 
the degree in which they are contracted or dilated, and 
to its own quantity, exercise a direct influence upon the 


104 LECTURE IV. 


adjoining cells. It might indeed be objected, with re- 
gard to the conditions of nutrition, that we have here 
to deal with quite a peculiar arrangement of the vessels, 
which are essentially of a venous nature, as being com- 
posed of ramifications of the portal and hepatic veins, but 
the hepatic artery also enters into the formation of this 
capillary network, so that the blood in it cannot be 
resolved into its individual arterial and venous consti- 
tuents. Injections from each of the vessels named ulti- 
mately find their way into the same capillary network. 

In most parts, however, the relations do not present 
such a simple form as in the liver; considerable inter- 
spaces often separate the individual cells, and no incon- 
siderable quantities of these elements are enclosed in 
every capillary mesh. I show you here a second object 
derived from a fresh human bdrain—from a lunatic who 
died with his cerebrum ina highly hyperemic state. 


Fia. 29. 


RE 





The section has been made Cae the corpus striatum, 
which was of a deep red colour. You have a good view 
Fig. 29. Natural injection of the corpus striatum of a lunatic. a, a. Gaps desti- 


tute of vessels, and corresponding to the strands of nervous fibres which traverse the 
ganglion. 80 diameters. 


MUSCULAR COAT OF THE STOMACH. 105 


of the naturally injected vessels ; and the width of the 
individual meshes of the capillary network may be 
clearly seen. The section has been carried transversely 
through the corpus striatum, and at certain intervals 
large, roundish spots may be distinguished, which ap- 
pear dark by transmitted light (Fig. 29, a, a, a), but by 
reflected light and to the naked eye look white, and are 
formed by transverse sections of the nervous fibres 
which run in long strands towards the spinal marrow. 
The vessels scarcely penetrate into them. The rest of 
the mass, on the other hand, consists of the proper grey 
substance of the corpus striatum, within which a vascu- 
lar network with very fine meshes is distributed, the 
grey substance of the nervous centres being everywhere, 
both in their interior and in their cortical substance, dis- 
tinguished from the white by its greater vascularity. A 
few large vessels are observable in the object, giving off 
branches, the ramifications of which continually dimi- © 
nish in size, until at last they terminate in capillary net- 
works with very fine meshes. Still, however close this 
network may be, every element of the substance of the 
brain by no means comes into immediate contact with 
a capillary vessel. 

The third object is a very slightly magnified injected 
preparation from the mus- 
cular coat of the stomach, 
in which, with a high power, 
the direction of the muscu- 
lar fibres is indicated by 
fine longitudinal striz ; here esi 
the vessels form tolerably (ifaavwas 
regular networks, connect- 
ed with one another by 


Fie. 30. 





Fig. 30. Injected preparation from the muscular coat of the stomach of a rabbit, 
magnified 11 diameters. 


106 LECTURE IV. 


transverse anastomoses, and splitting up into smaller 
and smaller vessels, which form fine networks within 
the tissue, so that the whole of it is by this means map- 
ped out into a series of irregularly four-sided divisions. 
To each of the ultimate intervascular spaces is allotted 
a certain number of muscular elements, so that the ves- 
sels are in some parts in contact with the muscular 
fibres, whilst in others they lie at a greater distance 
from them. 

If we go on in this way examining the structure of the 
different organs and tissues, we pass from such as, when 
injected, seem to consist almost entirely of vessels, in 
time to those which contain scarcely any, and at last to 
such as really have none at all. This is most strikingly 
the case with the connective tissues, and the most im- 
portant amongst these are done and cartilage. Perfectly 
developed cartilage has no longer any vessels at all ; 
perfectly developed bone certainly contains vessels, but 
in a very variable degree. That perfectly developed 
cartilage contains no vessels, you will not, [ suppose, call 
upon me to convince you by any additional, special 
proofs, inasmuch as you have seen various prepara- 
tions of cartilage, in which not a trace of them was to 
be observed. (Figs. 6, 9,22.) I now place before you 
a piece of young cartilage, because you can see in it 
what the arrangement of the vessels in cartilage is at 
an earlier period. It is a section from the calcaneum of 
a new-born child, and in it the vessels run up from the 
already-formed central osseous mass into the cartilage 
which still remains. The preparation shows along the 
outermost surface of the cartilage the transition from it 
into the perichondrium, whilst the lower part of the sec- 
tion is taken from the border of the already-formed 
bone. From this part large vessels are seen running 
up and terminating in the middle of the cartilage by 


VESSELS IN CARTILAGE. 107 


the formation of loops and plexuses, as it were a tree 
of villi (Zottenbaum) in the cartilage, and very much 
resembling a villus of the chorion of the ovum. In fact, 
the vessels mount up into the cartilage from the nutrient 
artery of the bone, but only to a certain height. There 
they form real loops, and at length break up into a fine 


Fie. 31. 





plexus of capillaries, out of which veins are ultimately 
formed, and run out again pretty near the spot where 
the artery entered. But the whole of the rest of the 
mass consists of non-vascular cartilage, the corpuscles of 
which, with a low power, look like fine points. Thus 
there is a whole host of cartilage-corpuscles lying be- 
tween the terminal loops and the external surface, and 
the whole of this layer is therefore dependent for its 


Fig. 31. Section of cartilage from the caleaneum of a new-born child. €. The 
cartilage, with its cells indicated by fine points. P. Perichondrium and adjoining 
fibrous tissue. a. Inferior border very near to the line of junction between the 
cartilage and the bone, with the vascular loops ascending from the nutrient artery. 
b, 6. Vessels which make their way through the perichondrium in the direction of 
the cartilage. 11 diameters. 


108 LECTURE IV. 


nutrition upon the juice which exudes from the terminal 
loops and permeates the tissue, though to a trifling ex- 
tent also upon the materials which the scanty vessels of 
the perichondrium convey to it. The vessels which 
spring from the nutrient artery mark in all bones, at a 
tolerably early period, pretty exactly the limits to which 
the ossification subsequently proceeds, whilst the rem- 
nants of the cartilage which remain bordering upon the 
joint never contain vessels. 

With regard to the dones themselves, the disposition 
of their blood-vessels is in itself tolerably simple, but at 


Fig. 32. 


Ons 


ye) 
— 
~—2 


spy 
o* 





the same time very characteristic. If we examine the 
compact substance, we can usually, even with the naked 
eye, distinguish upon its surface small openings through 
which vessels enter from the periosteum. With a mode- 


Fig. 32. Longitudinal section from the cortex of a sclerotic tibia. a, a. Medullary 
(vascular [Haversian]) canals, between them the bone-corpuscles for the most part 
parallel; but at 6 (in transverse section) concentrically arranged, 80 diameters. 


BONE-CORPUSCLES. 109 


rately high power we discover that these vessels (Fig. 
32, a) immediately beneath the surface form a network 
with somewhat long meshes, or a series of tubes anasto- 
mosing with one another and, generally speaking, run- 
ning longitudinally, for though they sometimes take a 
somewhat more oblique course inwardly, they still 
essentially maintain a longitudinal direction. Between 
these meshes there remain comparatively wide inter- 
spaces, within which, precisely as we before saw the 
cartilage cells, we here see the bone-corpuscles, and 
indeed also in a longitudinal direction, parallel to the 
surface. If the same part be examined in transverse 
section, we of course see, where the longitudinal canals 
were previously observed, nothing but their transverse 
sections here and there united by oblique communica- 
tions! Between them lies the proper osseous tissue, 
deposited in lamellar layers, some of them parallel to 


Fig. 33. 





the surface, some concentrically arranged around the 
vessels. In the deeper layers of the compact substance 


Fig. 38. Section of bone. a. Transverse section of medullary (vascular [Haver- 
sian]) canal, around which the concentric lamella, 7, lie with bone-corpuscles and 
anastomosing canaliculi. 1. Lamelle divided longitudinally and parallel. i. Irre- 
gular arrangement in the oldest layers of bone. v. Vascularcanal. 280 diameters. 


110 LECTURE IV. 


this concentric arrangement around the vessels con- 
stantly prevails. 

Between these more lamellated parts is left a small 
quantity of osseous substance (Fig. 33, 7) which does not 
present the same structure, but is arranged upon another, 
and independent, plan. Upon more accurate examina- 
tion it is seen to be formed of little columns, which are 
generally perpendicular to the long axis of the bone, but 
sometimes curve round, and so become parallel to the 
long axis. These are the remains of the spicula first 
formed during the growth of the bone in thickness, and 
are therefore of older date. 

As in the sections which are obtained by grinding 
down bone, the vessels themselves cannot for the most 
part any longer be distinguished, the cavities [Haversian 





canals] (Fig. 32, a, 33, a, v,) in which they run have 
been named medullary canals, improperly, inasmuch as 


Fig. 34. Bone-corpuscles from a morbid formation of bone in the dura mater of 
the brain. Their branching and anastomosing prolongations (canaliculi) are seen, 
as well us minute spots upon their walls, marking the funnel-shaped commence- 
ments of the canaliculi, 600 diameters, 





VASCULAR CANALS OF BONES. 111 


there is usually no marrow contained in these narrow 
channels ; they should properly be called vascular canals ; 
still the other term is so universally received, that it is 
even employed in cases where the wall of the vessel is in 
immediate contact with the internal surface of the cavity. 
Immediately surrounding these canals we see a series of 
peculiar structures; oblong or roundish bodies which 
usually appear black when the object is not fully brought 
into focus, and are provided with jaggs or processes. 
They used to be called bone-corpuscles, and their pro- 
cesses bone-canals (canaliculi ossei); and as the view 
was originally entertained that the calcareous matter 
was really deposited in them, and that the dark appear- 
ance which they usually present when viewed by trans- 
mitted light resulted from.the presence of this matter, 
the canals were also termed canaliculi chalicophori, a 


name which has now been altogether abandoned, because — 


convincing proofs have been obtained that, so far from 
being contained in them, the lime is, on the contrary, 
diffused throughout the homogeneous basis-substance 
which lies between them. 

As soon as this discovery was made, that, namely, the 
distribution of the lime in the osseous tissue took place 
in a manner just the reverse of that in which it had been 
supposed it did, the other extreme was immediately run 
into, and for the name of bone-corpuscles that of bone- 
cavities (lacunze) was substituted, and it was assumed 
that bone contained nothing but a series of empty cavi- 
ties and canals, which were indeed penetrated by a 
fluid, but still were really nothing more than fissures in 
the bone. Some few observers indeed actually called 
them bone fissures NowI have endeavoured to demon- 
strate in various manners that they are real corpuscles, 
and not mere cavities in a dense basis-tissue, but struc- 
tures provided with special walls and boundaries of their 


Rone 


how if Ud 


t Chit, 


119 LECTURE IV. 


own, which separate them from the intermediate sub- 
stance. or by the help of chemical reagents (concen- 
trated mineral acids, and particularly hydrochloric acid) 
we are enabled, by dissolving the basis-substance, 
namely, to disengage the corpuscles from it. In this way 
we furnish, I think, the most complete demonstration 
that they are really independent structures. Besides, a 
nucleus may be distinguished within these bodies ; and, 
even without entering into the history of their develop- 
ment, we discover that here too we have once more to 
deal with cellular elements of a stellate form. Bone 
therefore exhibits in its composition a tissue, containing, 
in an apparently altogether homogeneous basis-substance, 
peculiar, stellate bone-cells distributed in a very regular 
manner. 

The intervals which exist between every two of the 
vessels in bone are often very considerable ; whole sys- 
tems of lamella, beset with numerous bone-corpuscles, 
thrust themselves in between the medullary canal. Here 
it is certainly difficult to conceive the nutrition of so 
complicated an apparatus to depend upon the action of 
vessels some of them so remote, and especially so, to un- 
derstand how every individual particle of this extensive 
compound mass can manage to maintain a special rela- 
tion of nutrition to the vessels. For experience shows 
us that every single bone-corpuscle really possesses con- 
ditions of nutrition peculiar to itself. 

I have laid these details before you, in order to point 
out to you the gradual transition which takes place from 
the vascular and abundantly vascular, to the scantily 
vascular and non-vascular parts. If we would form a 
simple conception of the conditions of nutrition, I think 
we must lay it down as a logical principle, that what- 
ever 1s enunciated with regard to the nutrition of very 
vascular parts, must also hold good for that of scantily 


DEPENDENCE OF TISSUES UPON THE VESSELS. 113 


and non-vascular parts; and that, if the nutrition of 
individual parts is considered to be directly dependent 
upon the vessels or the blood, it must at all events be 
demonstrated that all the elements which stand in im- 
mediate connection with one and the same vessel, and 
are assigned to a single vessel for their support, present 
conditions of life essentially similar. In the case of bone 
it would be necessary to show that every system of 
lamellee which has only one vessel for its nutrition, 
always exhibits a similar state of nutrition. For if that 
vessel, or the blood which circulates in it, be the active 
agent concerned in the nutrition, the utmost that can be 
admitted is, that one part of the elements may be more, 
another less, subjected to their influence ; but still it 
must essentially be a common and similar influence 
which they experience. That this is no unreasonable /2/ iM 
requirement, that a certain dependency of definite terri- / ¢/o/" 
tories of tissue upon definite vessels must tects nk cs 
be admitted, the most.beautiful illustrations are afforded “*“"’, 
us in the doctrine of metastases, in the study of the 
changes which are effected by the occlusion of single 
capillary vessels, and with which we have become ac- 
quainted from the history of capillary embolia. In such 
cases, in fact, we see that a whole portion of tissue, as 
far as its immediate connection with a vessel extends, in 
its pathological relations also constitutes a whole—a vas- 
cular unity. But this vascular unity to a finer appre- 
hension still appears a compound, and it is not sufficient 


to split up the body into vessel-territories (Gefissterri- 
torien) alone, but within them a further division must be 


made into cell-territories (Zellenterritorien). 

This view has, I think, been essentially furthered by 
our having discovered, as I lately pointed out to you (p. 
76), the existence of a special system of anastomosing ele- 


ments in the connective-tissues, and by our having in 
8 


(A 


114 LECTURE IV. 


this manner filled the place of the vasa serosa (which the 
older writers imagined as a complement to the capilla- 
ries for these ultimate purposes of nutrition) with some- 
thing definite, by means of which the circulation of nu- 


tritive juices is rendered possible in parts which are in 


themselves poor in vessels. To keep to bone, we should 


Fig. 35. 





scarcely be justified in assuming the existence of vasa 
serosa in it. The hard basis-substance is throughout 


' Fig. 35. Section of an osseous plate from the arachnoid of the cerebrum, but 
quite normal in its structure. A branching vascular (medullary) canal is seen with 
canaliculi opening into it, and leading to the bone corpuscles. 350 diameters, 


NUTRITION OF BONE. 115 


uniformly filled with calcareous salts, so uniformly indeed, 
that no interval can be perceived between the indivi- 
dual calcareous particles. Though some few writers 
have assumed that little granules can be distinguished in 
it, this is an error. The only differentiation which can 
be seen is caused by the prolongation into the basis-sub- 
stance of the canaliculi, which all ultimately lead back to 
the bodies of the bone-cells (bone-corpuscles) and in 
their turn give out branches. ‘The peripheral extremi- 
ties of these little branches or processes extend right up 
to the surface of the vascular (medullary) canal. They 
are therefore inserted exactly where the membrane of 
the vessel begins (Fig. 35), for they can be distinctly 
perceived as very minute orifices upon the wall of the 
canal. Now since the different bone-corpuscles are in 
their turn distinctly connected with one another, means 
are afforded by which a certain quantity of juice taken 
up from the surface of the vascular canal is not diffused 
throughout the whole mass of tissue, but confined to 
these delicate, continuous, and specially provided chan- 
nels, and forced to move onwards in canals which are 
inaccessible to injections from the vessel. for a time it 
was believed that the canaliculi could be injected from 
the vessel, but this is only possible when the vascular 
canal has become empty by maceration. 

This is a condition precisely similar to what we 
observe in the teeth, in which the canaliculi can be in- 
jected from the pulp-cavity when empty. If a solution 


of carmine be injected into this cavity, the dental canali- ~~ 


culi are displayed in the form of numerous tubules run- 
ning up to the surface side by side in a radiated manner. 
The substance of the teeth also forms a tolerably broad 
layer of non-vascular material. Vessels are found no- 
where but in the pulp-cavity, in proceeding from which 
outwards we find nothing but the proper substance of 


116 LECTURE IV. 


the tooth (dentine) with its system of tubes, which ex- 
tend nearly up to the surface, and in the root of the 
tooth are directly continuous with a layer of real bony 
substance (cement) the corpuscles of which are seated 
upon the ends of the tubes. A provision for the con- 
veyance of the juices similar to that which in bone ori- 
ginates in the marrow, here takes its rise in the pulp, 
whence the nutritive fluid can be conveyed up to the 
surface by the means of tubes. 

These systems of tubes which are found in such a very 
marked form in bone and the teeth, are to be seen with 
far less distinctness in the soft structures, and it is chiefly 
for this reason, I imagine, that the analogy which exists 
between the soft connective tissues and the hard texture 
of bone has not been clearly comprehended. These sys- 
tems are most distinctly seen in parts which are more of a 
cartilaginous nature, as, for example, in fibro-cartilage. 
But it is a fact of great significance that we find a series 
of transitional forms between cartilage and the other 
connective tissues, in which the same conditions are con- 
stantly repeated. In the first place, parts which chemi- 
cally belong to the class of cartilages, for example, the 
cornea, which yields chondrine when boiled, although 
nobody regards it as real cartilage. But more striking 
is the arrangement in those parts in which the external 
appearance speaks in favour of a cartilaginous nature, 
but the chemical properties do not correspond, as for 
example, in the semi-lunar cartilages (Bandscheiben) of 
the knee-joint, which are interposed between the femur 
and tibia for the purpose of protecting the articular 
cartilages from too violent contact. These parts, which 
even now are generally described as cartilage, yield no 
chondrine on boiling, but gelatine ; and yet, in this hard 
connective tissue, we meet with the same system of anas- 
tomosing corpuscles that prevails in the cornea and in 


CANALS IN THE SEMI-LUNAR CARTILAGES. 117 


fibro-cartilage, and it is displayed with unusual distinct- 
ness and clearness. Vessels are almost entirely wanting 
in these cartilages, but in ex- 
change they contain a system 
of tubes of rare beauty. On 
making a section, we see that 
the whole is in the first place 
mapped out into large divi- 
sions, exactly like a tendon ; 
these are subdivided into 
smaller ones, and these are 
pervaded by a fine, stellate 
system of tubes, or, if you 
will, of cells, inasmuch as the 
notion of a tube and that of a 
cell here quite coincide. The 
networks of cells which here 
form the system of tubes, terminate externally in the septa 
bounding the individual divisions, and we here see in close 
proximity considerable collections of spindle-shaped cells. 
In these cartilages, too, the whole mass of tissue is only 
connected by its exterior with the circulatory system ; 
everything that penetrates into the interior must pass 
by a very circuitous route through a system of canals 
with numerous anastomoses, and the nutrition of the in- 
ternal parts is altogether dependent upon this mode of 
conveyance. The semi-lunar cartilages are structures of 
considerable extent and great density, and as they are 
entirely dependent for their nutrition upon this ultimate, 
minute system of cells, we have in them, much more 


Fig. 36. 





Fig. 86. Section from the semi-lunar cartilage of the knee-joint’ of a child. a. 
Bands of fibres, with spindle-shaped, parallel and anastomosing cells (seen in longi- 
tudinal section). 6. Cells, forming a network, with broad, branching, and anasto- 
mosing canaliculi (seen in transverse section). Treated with acetic acid. 350 
diameters. 


118 LECTURE IV. 


than in cartilage, to deal with such an arrangement for 
the supply of nutritive juices, as cannot be under the 
direct control of the vessels. 

For the sake of elucidation, I will merely add that the 
ultimate elements are seen to consist of very delicate 
cells, which are prolonged into fine filaments, that in 
their turn ramify, and look, when cut across, like small 
points in which a clear centre can be recognised. The 
filaments can ultimately be very distinctly traced back to 
the common cell just asin bone. They are extremely 
fine tubes which are intimately connected with one an- 
other, only that here they are in certain spots collected 
into large groups, by means of which the conveyance of 
the nutritive juice is principally effected, and that the 
intercellular substance in no instance becomes infiltrated 
with lime, but always preserves its character as connec- 
tive tissue. 


Te Br GT deo Vs 


FEBRUARY 27, 1868. 


NUTRITION, AND CONVEYANCE OF THE NUTRITIVE JUICES. 


Tendons—Cornea—U mbilical ayer 

Elastic tissue—Corium. 

Loose connective tissue—Tunica dartos, 

Importance of cells in the special distribution of the nutritive juices. 


ALLow me, gentlemen, as a supplement to what we 
saw and discussed in the preceding lecture, to lay before 
you a few more preparations in illustration of that pecu- 
liar species of nutritive arrangement which we have 
already seen to exist in various tissues, and which, I 
hope, will appear to you of very great importance in 
pathological processes also. 

You will remember that the last object of our con- 
sideration was a ligamentous disc (Bandscheibe), as it 
occurs in its most marked form in the knee-joint in the 
so-called semi-lunar cartilages, which are really no car- 
tilages at all. On the contrary, they possess the qualities 
of a flat tendon, and the individual structural relations 
which we found in them, are repeated throughout the 
whole of the transverse section of a tendon. 

We have to-day a series of objects from the tendo 
Achillis, both of the adult and the child, displaying the 


different stages of its development ; and as this is, more- 
119 


120 LECTURE V. 


over a tendon which is of importance in more than one 
way in an operative point of view, I may, I am sure, be 
excused for speaking a little more at length concern- 
ing it. 

On the surface of a tendon we see, as you well know, 
with the naked eye, a series of parallel, whitish strize 
which run pretty close to one another in a longitudinal 
direction, and give rise to the characteristic glossy ap- 
pearance. In a microscopical longitudinal section these 
strie lie farther apart, so that the tendon presents a 





somewhat fasciculated appearance and looks less homo- 
geneous than on the surface. This becomes much more 
evident in a transverse section, in which a series of 


Fig. 37. Transverse section from the tendo Achillis of an adult. From the sheath 
of the tendon, septa are seen at a, 6, and c, running inwardly, and uniting into a 
network so as to form the boundaries of the primary and secondary fasciculi. The 
larger ones (a and 6) generally contain vessels, the smaller ones (c) do not. Within 
the secondary fasciculi is seen the delicate network formed by the tendon-corpus- 
cles (reticulating cells—Netzzellen), or the intermediate system of juice-conveying 
canals (Saftkanalsystem), 80 diameters. 


TENDONS. - 121 


smaller and larger divisions (bundles, fasciculi) are 
offered to the view. 

On magnifying the object, an internal arrangement is 
shown almost exactly corresponding to that which we 
have observed in the semi-lunar cartilages. Externally, 
the tendon is invested in its whole circumference by a 
fibrous mass, in which the vessels are contained, that are 
entwined around the tendon. From these at different 
points vessels proceed into the interior, where they are 
to be seen in the larger partitions which separate the 
fasciculi (Fig. 37, a); but into the interior of the fasci- 
culi themselves no trace of a vessel enters, any more 
than it does into the interior of the semi-lunar cartilages ; 
there, on the contrary, we again meet with the network 
of cells we have been talking about, or, in other words, 
the peculiar system of juice-conveying canals of which 
we lately considered the import in bone. 

Tendons may therefore in the first place be divided 
into larger (primary) bundles, and these in their turn 
into a certain number of smaller (secondary) fasciculi, 
which are separated by broadish bands of a fibrous sub- 
stance containing vessels and fibre-cells, so that a trans- 
verse section of a tendon presents a meshed appearance. 
From this intervening substance, which must not, how- 
ever, be regarded as a tissue of a peculiar description, 
there pass into the interior of the fasciculi stellate cells 
(tendon-corpuscles) which anastomose with another and 
establish a communication between the external vascular, 
and the internal non-vascular, parts of the fasciculi. 
This relation is, of course, much more evident in the 
tendons of children than in those of adults. The older 
the parts become, namely, the larger and finer do the 
processes of the cells in general become, so that in many 
sections we do not meet with the real bodies of the cells, 
but only see minute speck , which, by altering the focus, 


122 LECTURE Y. 


may be traced into filaments—or point-like orifices. 
The individual cells, therefore, come to be more widely 


Fig. 38. 























separated, and it becomes more and more difficult to 
obtain a view of the whole of a cell at once. Besides, 
we must first obtain a clear notion of the relation be- 
tween a longitudinal and a transverse section. Where, 
namely, in a longitudinal section, there are spindle- 
shaped cells, in a transverse section will be seen stellate 
ones, and to the network of cells displayed in the trans- 
verse section corresponds the regular succession of 
spindle-shaped corpuscles, arranged in rows which we 
see in a longitudiual section, entirely in correspondence 
with the plan which we have shown to be followed in 
connective tissue. The cells, therefore, are here also 
only apparently simply spindle-shaped, when an exactly 
longitudinal section is examined; but if it has been 


Fia. 38. Transverse section from the interior of the tendo Achillis of a new-born 
child. a. The intervening mass which separates the secondary fasciculi (corres- 
ponding to Fig. 37, c), and entirely composed of densely aggregated spindle-shaped 
cells. Directly anastomosing with these, we see on both sides at 6, 6, reticulating 
and spindle-shaped cells running into the interior of the fasciculi. 300 diameters. 


TENDONS—THEIR NUTRITION. : 193 


made a little obliquely, the lateral processes are per- 
ceived, by means of which the cells of one row commu- 
nicate with those of another. 


Fie. 39. 





Up to the present moment the progress of the growth 
of tendons after birth has not been made the subject of 
a regular investigation, and it is unknown whether any 
further multiplication of the cells takes place in them ; 
this much, however, is certain, that the cells in many 
places afterwards become much elongated, and the inter- 
vals between the individual nuclei extremely great. 
The actual structural relations, however, do not thereby 
experience any change ; the original cells also continue 
members of the great system of tubes, which in the per- 
fectly developed tendon pervades the whole tissue. 


Fig. 39. Longitudinal section from the interior of the tendo Achillis of a new- 
born child. a, a, a. Intervening bands. 6, b. Fasciculi. In both we see spindle- 
shaped, nucleated cells, partially anastomosing, with an inter-cellular substance 
slightly striated in a longitudinal direction, the cells being more crowded in the 
bands, and less numerous in the fasciculi. c. Section of an interstitial blood-vessel. 
250 diameters. 


124 LECTURE 1g 


Hence we see how, although the tendon contains no 
vessels in its most internal parts, and, as may be ob- 
served in every case of tenotomy, receives but little 
blood by the external vessels of its sheath, and by the 
internal vessels of the septa between the larger fasciculi, 
it is possible, notwithstanding, for a uniform nutrition 
of the parts to take place. This we cannot imagine to 
be effected in any other way than by the distribution of 
nutritive juices in a regular manner throughout the 
entire substance of the tendon by means of special canals 
distinguishable from the vessels. The natural divisions 
of the tendon are, however, nearly entirely symmetrical, 
so that an equally large quantity of intercellular sub- 
stance falls to the share of every cellular element, and 
as the cell-networks in the interior can be directly 
traced into the dense bundles of cells of the septa, and 
these in their turn up to the vessels (Figs. 37, 38), we 
may, I think, unhesitatingly regard these reticulating 
cells as the channels for the transmission of this inter- 
mediate current of nutritive juice, which has no commu- 
nication by means of orifices with the general circu- 
lation. | 

You have here a fresh instance in support of my view 
with regard to cell-territories. I would parcel out the 
whole tendon, not into primary and secondary fasciculi, 
but rather into certain series of cells connected in a reti- 
form manner ; to each series, moreover, I would assign 
a certain district of tissue, so that in a longitudinal sec- 
tion, for example, about half of each band of basis-sub- 
stance would belong to one, the other half to another 
series of cells. What is, therefore, regarded as consti- 
tuting the proper fasciculi of the tendon, would, accord- 
ing to this view, have really to be split up, and the ten- 
don portioned out into a great number of nutritive 
districts (Hrnaihrungs-Territorien), 


CORNEA—UMBILICAL CORD. 125 


‘This is the condition which we everywhere find recur- 
ring in these tissues, and upon it will at the same time 
be found to depend, as I hope you will convince your- 
selves by direct observation, the size of the districts 
invaded by disease; every disease which essentially 
depends upon a disturbance in the internal disposition of 
the tissues is:always made up of the sum of the separate 
changes occurring in such territories. But at the same — 
time the pictures which are here offered to us afford a 
really zsthetical enjoyment through the delicacy of this 
arrangement, and I cannot deny that, as often as I look 
at a section of tendon, it is with a peculiar feeling of 
satisfaction that I contemplate these reticular arrange- 
ments, which effect a union between the exterior and 
the interior, and, excepting in bone, can in no structure 
be demonstrated with greater distinctness and clearness 
than in tendons. 

Considering the structure of the cornea and the dispo- 
sition of its parts, it would be most convenient, gentle- 
men, to proceed at once to. the consideration of its his- 
tory, still I prefer reverting to it hereafter, inasmuch as 
it is at the same time the most suitable object for the 
demonstration of pathological changes. I will therefore 
only observe here, that in the same way that tendons 
have their peripheral system of vessels, and that their 
internal parts are nourished by a delicate juice-convey- 
ing system of tubes, so also in the cornea only the most 
minute vessels extend a few lines over its border, so that 
the central parts are completely destitute of vessels, as 
indeed they were obliged to be, in order to allow of the 
sransparency of the tissue. 

I should like, on the other hand, in connection with 
the foregoing tissues, to speak of one which has gene- 
rally met with but little special preference in_ histology, 
but is perhaps more likely to have some interest in your 


126 LECTURE V. 


eyes, I mean the wmbzlical cord. Its substance (the so- 
called jelly (gelatina) of Wharton™) is also formed by 
one of those tissues which certainly contain vessels, but 
yet really possess none. The vessels which are trans- 
mitted through the umbilical cord, do not immediately 
contribute to its nourishment, at least not in the sense in 
which we speak of nutrient vessels in other parts. For 
when we speak of nutrient vessels, we always mean ves- 
sels which have capillaries in the parts which are to be 
nourished. The thoracic aorta is not the nutrient ves- 
sel of the thorax, any more than the abdominal aorta, or 
the vena cava, is that of the abdominal viscera. We 
should expect, therefore, in the case of the umbilical 
cord to find umbilical capillaries in addition to the two 
umbilical arteries and the umbilical 
vein. But these arteries and this 
vein run their course to the placenta, 
without giving off a single small 
vessel, and it is only when they have 
reached that body that they begin to 
ramify. The only capillary vessels 
which are found in the whole length 
of the umbilical cord of a somewhat 
developed foetus do not extend more 
than about four or five lines (in rare 
instances a little farther), beyond the 
abdominal walls into that part of the 
cord which remains after birth. The 


Fig. 40. 





Fig. 40. The abdominal end of the umbilical cord of a nearly full-grown foetus, 
injected. .A. The abdominal wall. £&. The permanent part of the cord with a 
congeries of injected vessels along its border. @. Its deciduous portion with the 
convolutions of the umbilical vessels. v. The limits of the capillaries. 


* Lympheeductus, vel gelatina, que eorum vices gerit, alterum succum albumini 
ovorum similorem abducit (a placenta) ad fyniculum umbilicalem. (Thom. Whart. 
Adenographia, Amsteledami, 1659, p. 233.) 











THE UMBILICAL CORD. 127 


farther up this vascular part extends, the greater the 
development of the navel. When the vascular layer is 
prolonged but a very short distance the navel is greatly 
depressed ; when it reaches a long way up, a prominent 
navel is the result. The capillaries mark the limits of 
the permanent tissue ; the deciduous portion of the cord 
has no vessels of its own. 

This condition, which seems to be of great importance 
as regards the theory of nutrition, can be very easily 
seen with the naked eye in injected foetuses of five 
months and upwards, and in new-born children. The 
vascular layer terminates by a nearly straight line. 

Preparations of this sort do not, to be sure, furnish 
absolute proof, for there might happen to be a few 
minute vessels proceeding farther up, but invisible to 
the naked eye. But I formerly made this very point 
the subject of special investigation, and although I in- 
jected a number of umbilical cords, some from the arte- 
ries, and others from the veins, I never succeeded in 
discovering a single collateral vessel, however minute, 
that passed the limits of the persistent layer. The whole 
of the deciduous portion of the umbilical cord, that long 
portion which lies between its cutaneous end and its ter- 
mination in the placenta, is entirely destitute of capilla- 
ries, and there really exist no other vessels in it than 
the three large trunks. Now these are all of them re- 
markable for the great thickness of their walls, which, 
as we have really only known since the investigations of 
Kélliker, are enormously rich in muscular fibres. 

In a transverse section of the umbilical cord it may be 
observed, that the thick middle coat of the vessels is 
entirely composed ot smooth muscular fibres, lying in 
immediate contact one with the other, and in such abun- 
dance as is scarcely to be seen in any completely 
developed vessel. This peculiarity explains the extra- 


128 LECTURE V. 


ordinary great contractility of the umbilical vessels, 
which can be so readily seen in action on a large scale 
when mechanical stimuli are applied, when the vessels 
are divided with scissors or are pinched, or after the 
employment of electrical stimuli. Sometimes, upon the 
application of external stimuli, they even contract to 
such a degree that their canal is entirely closed, and thus 
after birth, even without the application of a ligature, 
as when, for example, the umbilical cord has been torn 
asunder, the bleeding may stop of itself. The thickness 
of the walls of these vessels is, therefore, easily compre- 
hensible, for in addition to the muscular coat, which is 
of itself so thick, there is an internal, and, though it is 
certainly not very strongly developed, an external coat ; 
and only after this do we come to the gelatinous, jelly- 
like tissue (mucous tissue (Schleimgewebe) ) of the umbili- 
cal cord. Through these layers, therefore, nutrition 
would have to take place, if the umbilical vessels were 
the nutrient vessels of the cord. Now I certainly can- 


Fie. 41. 


iy mit ; 
i 


SEER 
wae 


ily 
st 


ay) 





Fig. 41. Transverse section through a part of the umbilical cord. On the left is 
seen the section of an umbilical artery, with a very thick muscular coat, and to this, 
as one proceeds outwards, succeeds the gradually widening network of cells of the 
mucous tissue of the cord. 80 diameters. 


THE MUCOUS TISSUE OF THE UMBILICAL CORD. 129 


not say with certainty whence the tissue of the umbilical 
cord derives its nourishment ; perhaps it receives nutri- 
tive matter from the liquor amnii, nor am I inclined to. 
deny the possibility of nutriments passing through the 
walls of the vessels, or of the onward conveyance of 
nutritive materials from the small capillaries of the per- 
sistent portion. In any case, however, a large extent of 
tissue lies at a distance from all vessels and from the 
surface, and is nourished and supported without the pre- 
sence of any minute system of blood-vessels in it. Fora 
long space of time, indeed, no one troubled himself any 
further about this tissue, because it was designated by 
the name of jelly, and thereby summarily ejected from 
the number of the tissues and thrust into the ambiguous 
group of mere accumulations of organic materials. I 
was the first to show that it is really a well-constructed 
tissue of a typical form, and that what constitutes the 
ielly in the more restricted sense of the term, is the. 
expressible part of the intercellular substance, after the 
removal of which there remains a tissue containing a 
delicate network of anastomosing cellular elements, simi- 
lar to that which we have seen to exist in tendons and 
other parts. A section through the external layers of 
the umbilical cord exhibits a structure bearing great 
resemblance to the external layers of the cornea ; first, 
an epidermoidal stratum, beneath it a somewhat denser 
dermoid layer, and then the Whartonian jelly, which 
corresponds in texture to the subcutaneous cellular tissue, 
and is in some sort equivalent to it. This has a pecu- 
liarly interesting bearing upon the tissues of a more 
advanced period, inasmuch as, by thus ranking the jelly 
with subcutaneous tissue, we at the same time establish 
its very close relationship to the vitreous body, which is 
the only remnant of tissue that, as far as I have until 


now been able to make out, persists in man in this con- 
9 


130 LECTURE V. 


dition of jelly. It is the last remnant of the embryonic 
subcutaneous tissue which in the development of the eye 
is inverted with the lens (which was originally epidermis, 
Pe 38). 

The proper substance of the umbilical cord consists of 
a reticulated tissue, the meshes of which contain mucus 
(mucin) and a few roundish cells, whilst its trabecule are 
composed of a striated fibrous substance. In this le 
stellate corpuscles, and when a good preparation has 
been obtained by treatment with acetic acid, a symme- 
trical network of cells is brought to view, which splits up 
the mass into such regular divisions, that by means of 
the anastomoses which subsist between these cells 
throughout the whole of the umbilical cord, a uniform 


Fia. 42. 





distribution of the nutritive juices throughout the whole 
of its substance is in this instance also rendered possible. 


Fig. 42. Transverse section of the mucous tissue of the umbilical cord, exhibiting 
the network formed by the stellate corpuscles, after the application of acetic acid 
and glycerine. 300 diameters. 


CONNECTIVE (CELLULAR) TISSUE. 181 


© 


I have up to the present time, gentlemen, brought to 
your notice a series of tissues all of which agree in con- 
taining either very few capillary vessels, or none at all. 
In all these cases the conclusion to be drawn seems to be 
very simple—that, namely, the peculiar cellular, canali- 
cular arrangement which they possess serves for the cir- 
culation of juices. It might, however, be supposed that 
this was an exceptional property, appertaining only to 
the non- or scantily-vascular and, generally speaking, 
hard, parts ; and I must therefore add a few words con- 
cerning the soft textures which possess a similar struc- 
ture. All the tissues which we have hitherto considered, 
belong, in accordance with the classification which I have 
already given you, to the series of connective tissues ; 
fibro-cartilage, fibrous or tendinous tissue, mucous tissue, 
bone and the teeth, must one and all be considered as 
belonging to the same class. But to the same category 
belongs also the whole mass of what has usually been 
included under the name of cellular tissue (Zellgewebe), 
and for which the name proposed by Johannes Miiller, 
connective tissue (Bindegewebe) is the most appropriate ; 
that substance, which fills up the interstices in the most 
different organs, sometimes in greater, sometimes in less, 
quantity—which renders the gliding of parts one upon 
the other possible, and formerly was imagined to enclose 
considerable spaces (cells in an inexact sense of the 
word), filled with a gaseous vapor or with moisture. 

Of this kind is the peculiar interstitial, or connective, 
tissue, such as we meet with in the interior of the larger 
muscles between the several primitive fasciculi and in a 
still larger quantity between the several parcels, or 
bundles, of primitive fasciculi. Numerous arteries, 
veins, and capillaries lie in it; and the arrangements for 
its nutrition are the most favorable that.can be imagined, 
Notwithstanding this, however, there exists in it also, in 


a 
' 
form ered 


liad Uke 


139 LECTURE V. 


addition to its blood-vessels, a more delicate system of 
nutrient channels, precisely similar to that with which 
we have just become acquainted ; only that, wherever it 
is specially required, in particular parts a peculiar 
change takes place in the cells, the place of the simple 
cell-networks and -fibres being gradually occupied by a 
more compact structure, which originates in a direct 
transformation of them, namely, the so-called elastic 
tissue . 

A few months after I had made known my first obser- 
vations eoncerning the systems of tubes existing in the 
connective tissues, Donders published his concerning the 
transformation of the cells of connective, into the ele- 
ments of elastic, tissue—a discovery which has essen- 
tially contributed to the completion of the history of 
connective tissue. If this tissue, namely, be examined 
at points where it is liable to be much stretched, and 
where consequently it must be endowed with great power 
of resistance, the elastic fibres will be found arranged 
and distributed in it in the same way that the cells and 


Fig, 43. 





Fig. 43. Elastic networks and fibres from the subcutaneous tissue of the abdomen 
ofa woman. a, a. Large elastic bodies (cell-bodies), with numerous anastomosing 
processes. 6,6. Dense elastic bands of fibres, on the border of larger meshes. c, ¢. 
Moderately thick fibres, spirally coiled up at the end. d, d. Finer elastic fibres, at e 
with more minute spiral coils. 300 diameters. 


FIBRES OF ELASTIC TISSUE. 1338 


cell-tubules of connective tissue usually are, and the 
transformation of these latter into the former can gradu- 
ally be traced with such distinctness, that there remains 
no doubt, that even the coarser elastic fibres directly 
result from a chemical change and condensation of the 
walls of the cells themselves. Where originally there 
lay a cell, provided with a delicate membrane and 
elongated processes, there we see the membrane gradu- 
ally increasing in thickness and refracting the light more 
strongly, whilst the proper cell-contents continually 
decrease and finally disappear. The whole structure 
becomes in this way more homogeneous, and to a certain 
extent sclerotic, and acquires an incredible power of 
resisting the influence of reagents, so that it is only 
after long-continued action that even the strongest 
caustic substances are able to destroy it, whilst it com- 
pletely resists the caustic alkalies and acids in the 
degree of concentration usually employed in microscopi- 
cal investigations. The farther this change advances, 
the more does the elasticity of the parts increase, and in 
sections we usually find these fibres not straight or 
elongated, but tortuous, curled up, spirally coiled, or 
forming little zigzags (Fig. 43, c, e).. These are the 
elements which in virtue of their great elasticity cause 
retraction in those parts in which they are found in con- 
siderable quantity, as, for example, in the arteries. 
The fine elastic fibres, which are those that possess the 
greatest extensibility, are usually distinguished from the 
broader ones which certainly do not present themselves 
in tortuous forms. As far as regards their origin, how- 
ever, there seems to be no difference between the two 
kinds ; both are derived from connective-tissue cells, 
and their subsequent arrangement is only a reproduction 
of the original plan. In the place of a tissue, consisting 
of a basis-substance and anastomosing, reticulated cells, 


134 LECTURE V. 


there afterwards arises a tissue with its basis-substance 
mapped out by large elastic networks with extremely 
compact and tough fibres. | 

It has not up to the present time positively been 
determined, whether in the course of this transformation 
the condensation (sclerosis) of the walls of the cells pro- 
ceeds to such a pitch as entirely to obliterate their 
cavity, and thus completely destroy their powers of 
conduction, or whether a small cavity remains in their 
interior. In transverse sections of fine elastic fibres, 
it looks as if the latter were the case, and there is 
therefore ground for the supposition, that in the trans- 
formation of the corpuscles of connective tissue into 
elastic fibres, nothing more than a condensation and 
thickening, and at the same time a chemical metamor- 
phosis of the membrane, takes place, but that ultimately, 
however, a very small portion of the cell-cavity remains. 
What sort of a substance it is that constitutes the elastic 
parts, has not been determined, because it is not possible 
to accomplish their solution by any means; with a part 
of the products of the decomposition of this tissue we 
are, indeed, acquainted, but nothing further is known 
concerning its chemical constitution. But from this no 
decision can be arrived at with respect either to its com- 
position, or position in a chemical point of view with 
regard to other tissues. 

This kind of transformation prevails to an extraordi- 
nary extent in the skin, especially in the deeper layers 
of the corium proper, and to it is chiefly owing the 
extraordinary resistance of this tissue which we so 
gratefully acknowledge when daily testing it in the soles 
of our shoes. For the firmness of the individual layers 
of the skin depends essentially upon the greater or less 
quantity of elastic fibres contained in them. The most 
superficial part of the corium immediately beneath the 


ELASTIC TISSUE OF THE SKIN- 135 


rete mucosum is formed by the papillary portion (Papil- 
larkérper), by which we are to understand not only the 
papille themselves, but also a continuous layer of cori- 
aceous substance running along horizontally beneath 
them ; it is under this that the coarse elastic networks 
begin, whilst only fine elastic fibres, and these in a fasci- 
cular form, ascend into the papille themselves, at the 
base of which they begin to form fine and close-meshed 
networks (Figs. 16, P, P; 83, A,e; D,c). These latter 
are connected inferiorly with the very thick and coarse 
elastic network which pervades the middle and toughest 
portion of the skin, the corzwm proper ; below this comes 
a more coarsely meshed network within the less firm, 
but nevertheless very soltd, undermost layer of the cutis, 
which passes inferiorly into the adipose or subcutaneous 
tissue. — 
In the places where such a transformation into elastic 
tissue has taken place, there are trequently scarcely any 
distinct cells to be found. This is the case not merely 
in the skin, but also especially in certain parts of the 
middle coat of arteries, and particularly in the aorta. 
Here the network of elastic fibres attains such a prepon- 
derance, that it is only with great care that minute cellu- 
lar elements can here and there be detected. In the 
skin, on the other hand, in addition to the elastic fibres, 
a somewhat greater number of small corpuscles are 
found, which have retained their cellular nature, though 
they are certainly so extremely minute that they must ~ 
be specially sought for. They generally lie in the inter- 
stices of the large-meshed networks, where they either 
form a system with perfect anastomoses and small 
meshes, or else appear in the shape of more isolated, 
roundish bodies, in consequence of the individual cells 
not being very distinctly connected with one another. 
This is especially the case in the papillary portion of the 


136 ) LECTURE V. 


skin, which both in its continuous layer and in the 
papille contains nucleated cells, in direct contrast with 
the corium proper, which at the same time is less vascu- 
lar. Buta far greater number of vessels was certainly 
needed in the former part, inasmuch as they have at the 
same time to furnish nutritive material for the whole 


Fig. 44. 





stratum of cuticle which lies above the papilla ; never- 
theless, however, there is left only a small quantity of 
juice at the disposition of the papillae as such. Every 
papille, therefore corresponds to a certain (vascular) 
district of the superjacent cuticle, whilst on the other 
hand it is itself resolved into as many elementary (histo- 
logical) districts as there are elements (cells) in it. 

In the scrotum the subcutaneous tissue (the dartos) 
presents peculiar interest, from the fact of its being par- 
ticularly rich in vessels and nerves, quite in accordance 
with the peculiar import of the part; and besides from 
its possessing an enormous quantity of muscular tissue, 
consisting, in fact, of those little cutaneous muscles, 
which I lately described to you (p. 58). These are the 
really active elements of the contractile tunica dartos. 
In this very part in which formerly a contractile connec- 
tive substance was considered to exist, the quantity of 
the little cutaneous muscles is extremely large, and the 


Fig. 44. Vertical section from an injected preparation of the skin. #. Epider- 
mis. R. Rete mucosum. /P. Papille of the skin, with their ascending and 
descending vessels ( loops). C. Cutis, 11 diameters. 


THE DARTOS. 137 


ruge of the scrotum are produced solely and exclusively 
by the contraction of these minute fasciculi, which, espe- 
cially after they have been coloured with carmine, can 
very easily be distinguished from the connective tissue. 


Fig, 45, 





They are of pretty nearly the same breadth, broader for 
the most part than the bundles of connective tissue ; and 
in them the individual elements are arranged in the 
shape of long, smooth fibre-cells. Every muscular fasci- 
culus, after it has been treated with acetic acid, presents 
at regular intervals those peculiar, long, frequently 


Fig. 45. Section from the tunica dartos of the scrotum. Side by side and paral- 
lel are seen, an artery (a), a vein (v), and a nerve (x); the first two with small 
branches. On the right and left of them organic muscular fasciculi (m, m), and in 
the interspaces soft connective tissue (¢, c), with large anastomosing cells and fine 
elastic fibres. 300 diameters. 


138 LECTURE V. 


staff-shaped nuclei, and between them is seen a delicate 
division of the substance into separate cells, the contents 
of which have a slightly granular appearance. These 
‘are the wrinklers of the scrotum (corrugatores scrott). 
Besides, we also find in the extremely soft membrane a 
certain number of fine elastic elements, and in greater 
quantity the ordinary, soft, wavy connective tissue, with 
a great number of relatively voluminous, spindle-shaped 
and reticulated, granular, nucleated, cells. 

These persistent cells of connective tissue had pre- 
viously been totally overlooked, its fibrils having been 
regarded as its real elements. If, namely, the individual 
constituents of connective tissue be separated from one 
another, little bundles are obtained of a wavy form and 
streaky, fibrillar appearance. According to Reichert, 
indeed, this appearance is merely due to the formation 
of folds, an idea which ought not perhaps to be admitted 
to the extent in which it was advanced, but which has 
- not been altogether refuted, inasmuch as a complete iso- 
lation of the fibrils can never be effected excepting by 
artificial means. At all events a homogeneous basis- 
substance, which holds the fasciculi together, must be 
assumed to exist in addition to the fibrils. This, how- 
ever, is a question of subordinate importance. On the 
other hand, it is extremely important to know, that 
wherever this lax tissue is met with, whether beneath 
the cutis, in the interspaces of muscle, or in serous mem- 
branes, it is pervaded by cells which for the most part 
anastomose (so as in longitudinal sections to form paral- 
lel rows, in transverse ones networks), and separate the 
bundles of connective tissue from one another, in much 
the same way that the corpuscles of bone separate its 
different lamellae. In addition, the most manifold vascular 
connections are everywhere met with ; indeed, the ves- 
sels are so numerous, that a special nutrient canalicular 


THE DARTOS. 139 


system in the tissue might even appear altogether unne- 
cessary. But this tissue also, however favourably its 
capillary channels may be disposed, stands in need of an 
arrangement of such a nature as to render a@ special dis- 
trebution of the nutritive juices to the separate cellular dis- 
tricts possible. It is only when we conceive the absorp- 
tion of nutritive matter to be a consequence of. the 
activity (attraction) of the elements of the tissue them- 
selves, that we are able to comprehend how it is that 
the individual districts are not exposed every moment to 
an inundation on the part of the blood, but the proffered 
material is, on the contrary, taken up into the parts only 
in accordance with the requirements of the moment, and 
is conveyed to the individual districts in such a quantity, 
that in general at least, as long as any possibility of its 
maintenance exists, one part cannot be essentially de- 
frauded by the others. 


Tei Si Vee, 


MARCH 3, 1858. 


NUTRITION AND CIRCULATION. 


Arteries—Capillaries—Continuity of their membrane—-Its porosity—Hemorrhage 
by transudation (per diapedesin) —Veins—Vessels during pregnancy. 
Properties of the walls of vessels: 

1. Contractility -Rhythmical movement—Active or irritative hyperemia— 
Ischeemia—Counter irritants, 

2. Elasticity and its importance as regards the rapidity and uniformity of the 
current of blood—Dilatation of the vessels. 

3. Permeability—Diffusion—Specific affinities—Relations between the supply 
of blood and nutrition—Glandular secretion (liver)—Specific action of the 
elements of the tissues. 

Dyscrasia—Its transitory character and local origin—Dyscrasia of drunkards— 

Hemorrhagic diathesis—Sy philis. 


I HAVE endeavoured, gentlemen, in the last two lectures, 
to present to you a somewhat detailed picture of the 
more delicate arrangements which prevail in the body 
for the conveyance of the different currents of nutritive 
juices, and particularly for the conveyance of those cur- 
rents in which the juices themselves are more hidden 
from observation. Allow me to-day to pass on to the 
consideration of the larger channels and nobler juices, 
which, according to prevailing opinion, stand more in the 
foreground. 

The distribution of the blood takes place, as is well 
known, within the vessels in the following manner: The 


arteries divide into finer and finer branches, and whilst 
140 


ARTERIES. 141 


they thus divide, the character of their walls gradually 
undergoes such alterations, that at last minute canals, 
the so-called capillary vessels, appear, provided with a 
membrane as simple as any that is ever met with in the 
body. ‘The histological appearances which present them- 
selves in these different vessels are as follows: 

On isolating an artery we find that its walls are rela- 
tively very thick, and in those arteries which can be fol- 
lowed with the naked eye, not only. the well-known 
three coats are distinguished with the help of the micro- 
scope, but in addition to these, a fine epithelial layer, 
which invests the internal surface and is not wont to be 
included in the class of structures usually termed coats, 
The internal and external coats are essentially forma- 
tions of connective tissue, which in the larger arteries 
display a continually increasing quantity of elastic fibres ; 
between them lies the relatively thick middle, or circu- 
lar-fibre, coat, which, as being the seat of the muscular 
fibres, constitutes what may be almost termed the most 
important component of the arterial walls. These mus- 
cular fibres are found in the greatest abundance in the 
middle-sized and smaller arteries, whilst in the very 
large ones, and especially in the aorta, elastic layers form 
the predominant constituent even of the circular-fibre 
coat. In small arteries, on microscopical examination, 
there may be easily observed within this coat (Comp. 
Figs. 26, 6, 6; 45, a) little transverse striations, corres- 
ponding to the individual fibre-cells, and encircling the’ 
vessel in such dense array that we find fibre-cell by the 
side of fibre-cell without any interruption. The thick- 
ness of this layer can be readily estimated in conse- 
quence of the well-marked limits set to it upon the in- 
and out-side by the longitudinal-fibre coats; the only 
deceptive appearance is presented by certain round 
bodies, which are to be seen here and there in the sub- 


142 LECTURE VI. 


stance of the circular-fibre coat, but only at the border of 
the vessel (Figs. 26, 6, 6; 46.,m, m), and which look like 
round cells or nuclei scattered through the tissue. These 
are fibre-cells seen in apparent transverse section. The 

layer formed by the middle coat may be most distinctly 

seen, however, after the addition of acetic acid, which 

causes the appearance of a great number of oblong 

nuclei. 

It is this layer which, generally speaking, confers upon 
the arteries their specific character, and distinguishes 
them most clearly from the veins. There are, indeed, 
numerous veins in the body which possess considerable 
layers of muscular tissue—for example, the superficial 
cutaneous veins ; still, in the case of the smaller vessels, 
the occurrence of a distinctly marked circular-fibre coat 















































Fig. 46. 
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oe 
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is so peculiarly characteristic of arterial vessels, that, 
wherever we meet with such a structure, we are at once 


inclined to assume the vessel to be arterial. 
These vessels, which must be included among the 


Fig. 46. A minute artery from the sheath of the tendon of one of the extensors 
of a hand just amputated. a, a. External coat. m, m. Middle coat, with well- 
developed muscular layer. i, i. Internal coat, partly with longitudinal folds, partly 
with longitudinal nuclei, in the side-branch brought well into view in consequence 


of the two external coats having been torn away. 300 diameters. 


ARTERIES AND CAPILLARIES. 1438 


larger ones, although even when full of blood they only 
appear to the naked eye like red filaments, pass gradually 
into smaller ones, and with a power magnifying three 
hundred diameters, we see them breaking up into 
branches, into which, even when they are very small, the 
three coats are at first continued. It is only in the 
smallest branches that the muscular coat finally disap- 
pears, the intervals between the individual transverse 
fibres becoming wider and wider, and the internal coat 
(the nuclei of which lie ina longitudinal direction and 
cross those of the middle coat at right angles (Fig. 26, 
D, E,)), at the same time appearing more and more 
distinctly through it. The external coat also may be 
followed for a short distance farther (being in many 
places, as in the brain, rendered more evident by the in- 
terspersion of pigment or fat, Fig..26, D, £), till at last 
it also becomes lost to view, and only a simple capillary 
remains (Fig. 3, c). The general supposition, therefore, 
is that the proper capillary membrane most nearly cor- 
responds to the internal coat of the larger vessels, and it 
is usually considered that the more complete a vessel 
becomes, the greater is the number of the coats which 
develop themselves around it. The real developmental 
relations which these parts bear to one another have, 
however, been by no means accurately determined. 
Within the true capillary region there is nothing 
further worthy of notice in the vessels than the nuclei I 
have previously mentioned, which correspond to the 
longitudinal axis of the vessel, and are so imbedded in 
its membrane, that it is impossible to discover any traces 
of a surrounding cell-wall. The capillary membrane is 
seen to be quite uniform, absolutely homogeneous and 
continuous (Fig. 3, c). Whilst even as lately as twenty 
years ago, it was a matter of discussion whether there 
did not exist vessels which were destitute of true walls, 


144 LECTURE VI. 


and were nothing more than channellings or excava- 
tions in the parenchyma of organs, as well as whether 
vessels could not be produced by the formation of new 
tracks in communication with the old channels by the 
forcing asunder of the neighboring parenchyma; there 
can, at the present time, be no longer any doubt as to 
the vascular system’s being everywhere continuously 
closed by membranes. In these it is not possible to 
descry any porosity. Even the minute pores, which 
have recently been observed in different parts, have not, 
up to the present time, met with their counterparts in 
the capillary membrane, and when the porosity of this 
membrane is spoken of, the expression can only be 
admitted in a physical sense, as applying to invisible, 
really molecular interstices. A film of collodion is not 
more homogeneous, nor more continuous, than the mem- 
brane of a capillary. A series of possibilities, which 
used to be admitted, as that, for example, the continuity 
of the capillary membrane did not exist at certain points, 
simply fall to the ground. A ‘‘transudation”’ or dia- 
pedesis of the blood through the walls of vessels without 
the occurrence of any rupture cannot for an instant be 
admitted ; and although we cannot in every individual 
case point out the exact site of the rupture, it is, not- 
withstanding, quite inconceivable that the blood with its 
corpuscles should be able to pass through the walls in 
any other way than through a hole in them. ‘This is 
such a very natural deduction from ascertained histolo- 
gical facts, that all discussion upon the point is impos- 
sible. 

After the capillaries have pursued their course for a 
time, small veins begin gradually to form out of them, 
and generally run back in the neighbourhood of the arte- 
ries (Fig. 45, v). In them the characteristic circular- 
fibre coat of the arteries is in general wanting, or at least 





SMALL VEINS. 145 


it is very much less developed. In its place we find in 
the middle coat of the larger veins toughish layers, which 
are not characterized so much by the absence of muscu- 
lar elements as by the greater abundance of elastic ele- 
ments which run in a longitudinal direction and are 
found in greater or less quantity in different localities. 


Fig. 47. 





In an inward direction there follow next the softer and 
more delicate layers of connective tissue of the internal 


Fia. 48. 





Fig. 47. .A. Epithelium from the femoral artery (‘ Archiv f. path. Anat.,’ vol. iii., 
figs. 9 and 12, p. 596). a. Division of nucleus. 

B. Epithelium from veins of considerable size. a, a. Largish, granular, round, 
uni-nuclear cells (colourless blood-corpuscles?) 6, 6. Oblong and spindle- shaped 
cells, with divided nuclei and nucleoli. c. Large, flat cells, with two nuclei, of 
which each has three nucleoli, and is in process of division. d. Coherent epithe- 
lium, with the nuclei in a state of progressive division, one cell having six nuclei. 
320 diameters. 

Fig. 48. Epithelium from the vessels of the kidney. A. Flat, spindle-shaped 
cells with longitudinal folds and large nuclei from a new-born child. B. Ribbon- 
like, nearly homogeneous, plate of epithelium with longitudinal nuclei from an 
adult. 350 diameters. 

10 


146 LECTURE VI. 


coat, and lying on this is found, in the last place, a flat, 
extremely translucent layer of epithelium, which is very 
prone to protrude out of the cut end of the vessel, and 
gives the impression of spindle-shaped cells, so that it 
may easily be mistaken for spindle-shaped muscular cells. 
The smallest veins likewise possess this epithelium, but, 
with this exception, are, properly speaking, entirely com- 
posed of connective tissue provided with longitudinal 
nuclei (Fig. 45, v). 

These relations undergo no essential change even when 
the individual constituents of the vascular system expe- 
rience the most extreme enlargement. This is best seen 
in pregnancy, in which not merely in the uterus, but also 
in the vagina, the Fallopian tubes, the ovaries, and the 
ligaments of the uturus, both the large and small arteries 
and veins, as well as the capillaries, exhibit a very high 
degree of dilatation, so that the rest of the tissue, in spite 
of its having likewise in no inconsiderable degree become 
enlarged, is thereby virtually thrust into the back- 
ground. Nevertheless, however, parts of this puerperal 
sexual apparatus are extremely well adapted for display- 
ing the relation between the histological elements and 
the vascular (arterial) districts. In the fimbrie of the 
Fallopian tubes, for example, every plexus or loop 
formed towards the borders by the greatly dilated capil- 
laries encloses a certain number of large connective tis- 
sue cells, of which only a few lie in immediate contact 
with the vessels. In the ale vespertilionum we find, 
moreover, very beautifully displayed, a condition which 
is of frequent occurrence in the appendages of the gene- 
rative organs, and similar to what we lately considered 
in the scrotum; the vessels, namely, are accompanied 
by flat bundles of smooth muscle in considerable quan- 
tity which do not belong to them, but only follow the 
course of the vessels, and in part receive the vessels 





MUSCULAR ELEMENTS. 147 


into them. This is an extremely important feature, in- 
asmuch as the contraction of these ligaments, in which 
muscular tissue is not generally considered to exist, is 
by no means solely to be ascribed to the blood-vessels, 
as James Traer only a short time ago endeavoured to 
establish ; on the contrary, we find thickish, flat bundles 
of muscle which run through the middle of the liga- 
ments, and during menstrual excitement enable contrac- 
tions to take place, similar to those which we can follow 
with such great distinctness in external portions of the 
genital passages. 


If now the question be raised how far the individual 
elements of the vessels are of importance in the body, it 
is at once evident that the contractile elements play the 
most important part in the coarser processes of the cir- 
culation, whilst the elastic constituents come next, and 
the simply permeable, homogeneous membranes last. 
Let us first consider the import of the muscular elements, 
and more particularly in those vessels which are chiefly 
provided with them, namely the arteries. 

When an artery is acted upon by any influence which 
causes a contraction of its muscular tissue, it must of 
- eourse become narrower, inasmuch as the contractile 
cells lie in rings around the vessel ; this contraction may 
under certain circumstances proceed until the canal is 
almost entirely obliterated, and the natural consequence 
then is that less blood penetrates into the corresponding 
part of the body. When, therefore, an artery is in any 
way exposed to a pathological irritant, or when it is 
excited by some physiological stimulus, its proper action 
cannot be displayed in any other way than by its becom- 
ing narrower. Now, indeed, that the muscular elements 
of the walls of the vessels have become known, the old 
doctrine might again be taken up, that, namely, the vessels, 


148 LECTURE VI. 


like the heart, originated a kind of rhythmical pulsating 
movement, which was capable of directly furthering the 
onward movement of the blood, so that an arterial hyper- 
zmia would be the result of an increased pulsation in 
the vessels. 

We are indeed acquainted with one isolated fact which 
is a proof that a real rhythmical movement does take 
place in the arterial walls ; and this was first observed 
by Schiff in the ears of rabbits. Its rhythm, however, 
does not at all correspond with that of the well-known 
arterial pulsation ; the only counterpart to it exists in 
the movements which had previously been observed by 
Wharton Jones in the veins of the wings of bats, and 
proceed in an extremely slow and quiet manner. I have 
studied these phenomena in bats, and convinced myself 
that the rhythm coincindes neither with the cardiac nor 
the respiratory movements ; it is quite a peculiar, but 
comparatively not very forcible, movement, and takes 
place after tolerably long pauses, longer ones than. are 
observed in the case of the circulation and shorter than 
those which occur in respiration. In the ears of rabbits, 
also, the contractions of the arteries are far slower than 
the cardiac and respiratory movements. 

After excluding these phenomena, which manifestly 
ought not to be explained in such a way as to support 
the old view of the local occurrence of pulsation, the 
essential fact remains, that the muscular fibres of a ves- 
sel contract upon the application of every stimulus which 
sets them in action, but that this contraction is not pro- 
pagated in a peristaltic manner, but is confined to the 
spot irritated, or, at most, extends a little beyond, and 
continues for a certain length of time at this spot. The 
more muscular the vessel is, the more lasting and forcible 
is the contraction and the greater is the obstruction 
experienced by the current of blood. The smaller the 


CONTRACTION OF ARTERIES. 149 


vessels, the more rapidly, on the contrary, do we see the 
‘contraction succeeded by a dilatation, which, however, 
is not in its turn followed by a contraction, as it would 
have to be to constitute a pulsation, but persists for a 
longer or shorter time. This dilatation is not of an 
active, but of a passive nature, and results from the 
pressure of the blood upon the wall of the vessel which 
has become fatigued and opposes less resistance. 

If we now proceed to examine the phenomena which 


Fig. 49, 





Fig. 49. Irregular contraction of small vessels from the web of a frog’s foot after 
the application of stimuli. Copied from Wharton Jones. 


150 LECTURE VI. 


are usually grouped together under the title of active 
hyperemia, there can be no doubt but that the mus- 
cular tissue of the arteries is generally essentially con- 
cerned therein. We very commonly find we have to 
deal with processes in which the muscular fibres of the 
vessels have really been stimulated, and the contraction 
is succeeded by a state of relaxation, such as scarcely 
ever occurs in an equally marked manner in the rest of 
the muscles—a state which is manifestly the expression 
of a kind of fatigue and exhaustion, and is the longer 
persistent, the more energetic the stimulus which was 
applied. In small vessels with few muscular fibres, 
therefore, it often seems as if the stimuli really induced 
no contraction, in consequence of the extreme rapidity 
with which a state of relaxation is seen to set in, con- 
tinuing for a considerable time, and allowing of an in- 
creased influx of blood. 

This same condition of relaxation we can experiment- 
ally most easily produce by cutting the nerves supplying 
the vessels of a part, whilst the contraction can be 
effected to a very great extent by submitting these 
nerves to a very energetic stimulus. That our acquaint- 
ance with this kind of contraction is of so late a date, is 
explained by the fact that the stimuli applied to the 
nerves must be very powerful, and that, as Claude Ber- 
nard has shown, only strong electric currents are suffi- 
cient for the purpose. On the other hand, the condi- 
tions which ensue upon the section of the nerves are in 
most parts so complicated, that the dilatation escaped 
observation, until the lucky spot was discovered also by 
Bernard, and by the section of the sympathetic nerves 
in the neck a reliable and convenient field for observa- 
tion was thrown open to experiment. 

We obtain therefore the important fact that, whether 
the widening of the vessel, or, in other words, the 


ACTIVE HYPERAMIA. 151 


relaxation of its muscular fibres, be produced directly 
by a paralysis of the nerve or an interruption of the © 
nervous influence, or whether it be the indirect result of 
a previous stimulation, giving rise to exhaustion—that, 
I say, in every case we have to deal with a kind of 
paralysis of the walls of the vessel, and that the process 
is incorrectly designated active hypereemia, inasmuch as 
- the condition of the vessels in it is always a completely 
passive one. All that has been built up upon this 
assumed activity of the vessels, is, if not exactly built 
upon sand, still of an extremely ambiguous nature, and 
all the conclusions that have besides been drawn with 
regard to the important influence which the activity of 
the vessels was supposed to have upon the conditions of 
nutrition of the parts themselves, fall at the same time 
to the ground. 

‘When an artery is really in action, it gives rise to no 
hyperzemia ; the more powerfully it acts, the more does 
— it occasion anzemia, or, as I have designated it, zschemia, 
and the less or greater degree of activity in the artery 
determines the greater or less quantity of blood which 
in a unit of time can stream into a given part. The 
more active the vessel, the less the supply of blood. If, then, 
we have to deal with an hyperemia the result of irrita- 
tion, the most important point, therapeutically, is just 
this: to place the vessels in such a state of activity as 
will enable them to offer resistance to the onward rush 
of blood. This we can accomplish by means of what is 
called counter-irritation, a higher degree of irritation in 
an already irritated part, stimulating the fatigued mus- 
cular fibres of the vessel to persistent contraction, and 
thereby diminishing the supply of blood and leading the 
way to a regulation of the disturbance. In the very 
cases in which reaction, that is, regulatory activity, is 
most called for, the chief point is to overcome that state 


152 LECTURE VI. 


of passiveness which maintains the (so-called active) 
' hyperemia. 


If we now pass from the muscular to the elastic con- | 
stituents of the vessels, we meet with a property which 
is of very great importance, on the one hand in the 
veins, the activity of which is in many cases to be wholly 
referred to their elastic elements, on the other hand, in 
the arteries, and particularly in the aorta and its larger 
branches. In these the elasticity of the walls has the 
effect of compensating for the loss which the pressure of 
the blood experiences from the systolic dilatation of the 
vessels, and of converting the uneven current produced 
by the jerking movements of the heart into an even one. 
If the walls of the vessels were not elastic, the stream 
of the blood would unquestionably be rendered very 
much slower, and at the same time, pulsation would 
take place throughout the whole extent of the vascular 
apparatus as far as the capillaries, for the same jerking 
movement which is communicated to the biood at the 
commencement of the aortic system would continue even 
into the smallest ramifications. But every observation 
we make in living animals teaches us that within the 
capillaries the stream is a continuous one. This equable 
onward movement is effected by the elasticity of the 
walls of the arteries, in virtue of which they return the 
impulse which they receive from the in-rushing blood 
with the same force, and by this means maintain a regu- 
lar onflow of the blood during the time occupied by the 
following diastole of the heart. 

If the elasticity of the vessel be considerably dimin- 
ished, without its becoming stiff and immoveable (from 
calcareous incrustations) in the same degree, the dilata- 
tion, which it undergoes from the pressure of the blood, 
is not again compensated; the vessel remains in a 


ELASTICITY OF THE COATS OF VESSELS. 153 


dilated condition, and thus are gradually produced the 
well-known forms of ecstasis, such as we are familiar 
with in the arteries under the name of aneurysms, and 
in the veins under that of varices. In these processes, 
we have not so much, as has been represented of late, 
to deal with primary disease of the inner coat, as with 
changes which are situated in the elastic and muscular 
middle coat. 


If therefore it is the muscular elements of the arteries 
that have the most important influence upon the quan- 
tity of blood to be distributed, and the mode of its dis- 
tribution, in the several organs, and the elastic elements 
that are chiefly concerned in the production of a rapid 
and equable stream, they nevertheless exercise only an 
indirect influence upon the nutrition of the parts which 
lie outside the vessels themselves, and in this matter, we 
are obliged to betake ourselves, as a last resource, to the 
sumple, homogeneous membrane of the capillaries, without 
which indeed not even the constituents of the walls of 
the larger vessels provided with vasa vasorum would be 
able to maintain themselves for any lengthened period. 
The difficulty which here presents itself has, as you 
know, during the last ten years, been chiefly got over by 
the assumption of the existence of diffusive currents 
(endosmosis and exosmosis) between the contents of the 
vessels and the fluid in the tissues ; and by regarding the 
capillary wall as a more or less indifferent membrane, 
forming merely a partition between two fluids, which 
enter into a reciprocal relation with one another ; while 
the nature of this relation would be essentially deter- 
mined by the state of concentration they are in and their 
themical composition, so that, according as the internal 
or the external fluid was the more concentrated, the dif" 
fusive stream would run inwardly or outwardly, and, 


154 LECTURE VI. 


according to the chemical peculiarities of the individual 
juices, certain modifications would arise in these currents. 
Generally speaking, however, the chemical side of this 
question has been but little regarded. 

It cannot be denied that there are certain facts which 
cannot well be explained in any other manner, especially 
in cases where essential alterations have taken place in 
the state of concentration of the juices, for example, in 
that form of cataract which Kunde has artificially pro- 
duced in frogs by the introduction of salt into their intes- 
tinal canal or subcutaneous cellular tissue. But in pro- 
portion as, after a physical study of the phenomena of 
diffusion, the conviction has been acquired that the mem- 
brane which separates the fluids is not an indifferent 
substance, but that its nature exercises a directly con- 
trolling influence upon the permeating powers of the 
fluids, it becomes impossible that a like influence should 
be denied the capillary membrane. We must not, how- 
ever, go so far, as to ascribe to this membrane all the 
peculiarities observable in the interchange of material, 
and so explain how it happens, that certain matters 
which enter into the composition of the blood are not 
distributed in equal proportion to every part, but leave 
the vessels at some points in greater, at others in less, 
quantity, and at others not at all. These peculiarities 
depend, manifestly, on the one hand, upon the differ- 
ent degrees of pressure to which the column of blood is 
subjected in certain parts, and, on the other, upon spe- 
cial preperties of the tissues ; and we are irresistibly com- 
pelled, both by the consideration of simply pathological, 
and particularly by that of pharmaco-dynamical, pheno- 
mena to admit that there are certain affinities existing 
between definite tissues and definite substances, which 
must be referred to peculiarities of chemical constitution, 
in virtue of which certain parts are enabled in a greater 


INFLUENCE OF THE VESSELS UPON NUTRITION. 155 


degree than others to attract certain substances from the 
neighbouring blood. ; 

If we consider the possibility of such attraction with a 
little more attention, it is peculiarly interesting to ob- 
serve the behaviour of parts, which are at a certain dis- 
tance from the vessel. If we apply a definite stimulus, 
for example, a chemical substance, a small quantity of 
an alkali I will suppose, directly to any part, we see that 
this shortly afterwards takes up more nutritive matter, 
so that even in a few hours its size becomes considerably 
increased, and that, whilst before we were perhaps 
scarcely able to distinguish anything in its interior, we 
now find an abundant, relatively opaque material within 
it, in no wise composed of alkali which had made its way 
in, but essentially containing substances of an albuminous 
nature. Observation shows that the process in all vas- 
cular parts begins with hyperemia, so that the idea rea- 
dily presents itself that the hypersemia is the essential and 
determining cause. But if we investigate the matter 
more minutely, we find it difficult to understand how the 
blood, which is in the hyperemic vessels, can contrive 
only to act just upon the irritated part, whilst other 
parts lying in the immediate vicinity are not affected ‘in 
the same manner. In all cases in which the vessels are 
the immediate originators of disturbances which take 
place in a tissue, these are most marked in the immediate 
neighbourhood of the vessels and in the district which they 
supply (vascular (or vessel-) territory). If we introduce 
an irritating, as, for example, a decomposing body into 
a blood-vessel, a fact that has been established by me 
upon a large scale when tracing out the history of em- 
bolia, we by no means see that the parts at a distance 
from the vessel are the principal seats of active change, 
but that this is in the first instance manifested in the wall 
of the vessel itself and then in the adjoining histological 


156 LECTURE VI. 


elements. But if we apply the stimulus directly to the 
tissue, the central point of the disturbance will always 
continue to be that at which the stimulus produced its 
effect, just the same whether there are vessels in the 
neighbourhood or not. 

We shall hereafter have occasion to return to this sub- 
ject, and my only object here was to lay this fact before 
you in its general features, and thus repel the ordinary 
conclusion, which is as convenient as it is fallacious, that 
hyperemia (in itself passive) exercises a directly regulat- 
ing influence upon the nutrition of tissues. 

If a special proof were still required in order to com- 
plete the refutation of this assumption, which in an ana- 
tomical point of view is utterly untenable, we find a 
most apposite argument in the experiment above men- 
tioned of the section of the sympathetic. In an animal 
the sympathetic may be divided in the neck ; thereupon 
a state of hypersemia ensues in the whole of that half of 
the head, the ears become dark red, the vessels greatly 
dilated, the conjunctiva and nasal mucous membrane 
turgidly injected. ‘This may continue for days, weeks, 
or months, without the least appreciable nutritive dis- 
turbance necessarily arising therefrom; the parts, 
although gorged with blood, are yet, as far at least as 
we are at present able to judge of this, in the same state 
of nutrition as before. If we apply stimuli sufficient to 
produce inflammation to these parts, the only thing that 
we remark is, that the inflammation runs its course more 
quickly, without exhibiting either in itself or in the na- 
ture of its products anything essentially unusual. 

The greater or less quantity of blood, therefore, which 
flows through a part is not to be regarded as the only 
cause of the changes in its nutrition. There is, I sup- 
pose, no doubt that, when a part, which is in a state of 
irritation, receives more blood than usual, it is also able 


INFLUENCE OF THE VESSELS UPON NUTRITION. 157 


to attract a larger quantity of material from the blood 
with greater readiness than it otherwise would have 
done, or than it would be able to do, if the vessels were 
in a state of contraction or less filled with blood. If, 
therefore, it were to be objected to my view that in such 
conditions the most favorable effects are often produced 
by local abstractions of blood, this would be no proof of 
its incorrectness. If we cut off or diminish the supply 
of nutritive matter, we must, of course, prevent the part 
from absorbing more than its wont, but, vice versd, we 
cannot by offering it a larger quantity of nutritive mate- 
rial straightway compel it to take up more than it did ; 
these are two entirely independent cases. However apt 
one may be to conclude (and however much I may be 
disposed to allow, that at the first glance there is some- 
thing very plausible in such a conclusion) that, from the 
favourable effect which the cutting off of the supply of 
blood has in putting a stop to a process which arose from 
an increase of it, the process depended upon this increased 
supply, yet I am of opinion that the practical fact can- 
not be interpreted in this way. It is not so much an 
increase of quantity, either in the blood as a whole or in 
that portion of it contained in an individual part, which 
is required in order that a like increase should forthwith 
take place in the nutrition of that part, or of the whole 
body, as that, in my opinion, particular conditions should 
obtain in the tissues (irritation) altering the nature of 
their attraction for the constituents of the blood, or that 
particular matters should be present in the blood (specific 
substances), upon which definite parts of the tissues are 
able to exercise a particular attraction. 

If you apply this doctrine to the humoro-pathological 
conception of the processes, you will be able to deduce 
from it that Iam far from contesting the correctness of 
the humoral explanations in general, and that I rather 


158 LECTURE VI. 


cherish the conviction that particular substances which 
find their way into the blood are able to induce particu- 
lar changes in individual parts of the body by their be- 
ing taken up into them in virtue of the specific attraction 
of individual parts for individual substances. We know, 
for example, that a number of substances are introduced 
into the body which possess special affinities for the ner- 
vous system, and that among this number again there 
are some which stand in a closer connection with certain 
very definite parts of the nervous system, as for instance 
with the brain, the spinal cord or sympathetic ganglia, 
and others again with particular parts of the brain, spi- 
nal cord, etc. On the other hand, we see that certain 
materials have some special relation to definite secreting 
organs ; that they penetrate and pervade them by a kind 
of elective affinity ; that they are excreted by them ; 
and that, when there is a too abundant supply of such 
materials, a state of irritation is produced in these or- 
gans. But an essential condition in all these cases is, 
that the parts which are believed to have a particular 
elective affinity for particular matters, should really exist, 
for a kidney which loses its epithelium is thereby de- 
prived of its secreting power. Another condition is that 
the parts should possess a relation of affinity, for neither 
a diseased, nor a dead, kidney has any longer the affinity 
for particular substances which the gland, when living 
and healthy, possessed. The power of attracting and 
transforming definite substances can be maintained at 
most for a short time in an organ, which no longer con- 
tinues in a really living condition. We are therefore, in 
the end, always compelled to regard the individual ele- 
ments as the active agents in these attractions. An 
hepatic cell can attract certain substances from the blood 
which flows through the nearest capil’ary vessel, but it 
must in the first place exist, and in the next be in the 


SPECIFIC AFFINITIES—LIVER. 159 


ejoyment of its special properties, in order to exercise 
this attraction. If the living element become altered, if 
a disease set in which causes changes in its molecular, 
physical, or chemical peculiarities, then its power of ex- 
ercising this special attraction will at the same time also 
be impaired. 

Let us consider this example with still greater atten- 
tion. The hepatic cellsare almost in direct contact with 
the walls of the capillaries, from which they are only sepa- 
rated by a thin layer of delicate connective tissue. If 
now we were to imagine that the peculiar property pos- 
sessed by the liver of secreting bile, merely consisted in 
a particular disposition of the vessels of the organ, we 
should indeed in no wise be justified in doing so. Simi- 
lar networks of vessels, in a great measure of a venous 
nature, are found in several other places, for example, 
in the lungs. But the peculiarity of the secretion of bile 
manifestly depends upon the liver-cells, and only so long 
as the blood flows past in the immediate neighbourhood 
of the hepatic cells, does the particular attraction of mat- 
ter continue which characterizes the action of the liver. 

When the blood contains free fat, we see that after a 
time the hepatic cells take it up in minute particles, and 
that if the supply continues, the fat becomes more abun- 
dant and is gradually separated in the form of largish 
drops within the hepatic cells (Fig. 27, B, b). That 
which we see in the case of fat in a more palpable form, 
we must conceive to occur in the case of many other 
substances in a state of more minute division. Thus for 
the due performance of secretion it will always be essen- 
tial that the cells exist in a certain, special condition ; if 
they ‘become diseased, if a condition be developed in 
them connected with some important chemical change in 
their contents, for example, an atrophy, ultimately caus- 
ing the destruction of the parts, then the power pos- 


160 LECTURE VI. 


sessed by the organ of forming bile will at the same time 
continually become more limited. We cannot conceive 
a liver without liver-cells ; they are, as far as we know, 
the really active elements, since even in cases in which 
the supply of blood has become limited owing to obstruc- 
tion in the portal vein, the hepatic cells are able to pro- 
duce bile, although perhaps not in the same quantity. 

This fact derives peculiar value from its occurrence in 
the liver, because the matters which constitute the bile 
do not, as is well known, exist pre-formed in the blood, 
and we must therefore suppose the constituents of the 
bile to arise not by a process of simple secretion, but by . 
one of actual formation in the liver. This question has, 
as you are aware, recently become invested with a still 
greater degree of interest in consequence of the observa- 
tion of Bernard that the property of producing sugar is 
also inherent in these elements, whereby the blood is 
supplied upon so gigantic a scale with a substance which 
has the most decided influence upon the internal meta- 
morphic processes and upon the production of heat. If, 
therefore, we speak of the action of the liver, we can, 
both in regard to the formation of sugar as well as that 
of bile, mean nothing but the action of its individual ele- 
ments (cells), an action which consists in their attracting 
matters from the passing current of blood, in their effect- 
ing within their cavity a transmutation of these matters, 
and returning them in this transmuted form either to 
the blood, or yielding them up to the bile-ducts in the 
shape of bile. 

Now I demand for cellular pathology nothing more 
than that this view, which must be admitted to be true 
in the case of the large secreting organs, be extended also 
to the smaller organs and smaller elements ; and that, for 
example, an epidermis-cell, a lens-fibre or a cartilage-cell 
be, to a certain extent, admitted to possess the power of 


THE NOBLER JUICES. 161 


deriving from the vessels nearest to them (not always 
indeed directly, but often by transmission from a dis- 
tance), in accordance with their several special require- 
ments, certain quantities of material ; and again that, 
after they have taken this material up, they be held to. 
be capable of subjecting it to further changes within 
themselves, and*this in such a manner that they either 
derive therefrom new matter for their own development ; 
or that the substances accumulate in their interior, with- 
out their reaping any immediate benefit from it; or 
finally that, after this imbibition of material, even decay 
may arise in their structure and their dissolution ensue. 
At all events it seems necessary to me that great promi- 
nence should be assigned to this specific action of the ele- 
ments of tissues, in opposition to the specific action of the 
vessels, and that in studying local processes we should 
principally devote ourselves to the investigation of pro- 
cesses of this nature. 


It will now, I think, be most suitable for us next to 
enter a little more in detail upon the consideration of 
the facts which form the basis of the humoro-pathologi- 
cal system—upon the study of the so-called nobler juices. 
If the blood be considered in its normal influence upon 
nutrition, the most important point is not its movement, 
nor the greater or less afflux of it, but its intimate com- 
position. When the quantity of blood is great, but its 
composition does not correspond to the natural require- 
ments of the parts, nutrition may suffer ; when the quan- 
tity is small, nutrition may proceed in a comparatively 
very favourable manner, if every single particle of the 
blood contain its ingredients mixed in the most favorable 
proportions. 7 

If the blood be considered as a whole in contradistine- 


tion to other parts, the most dangerous thing we can do 
11 


162 LECTURE VI. 


is to assume what has at all times created the greatest 
confusion, namely, that we have in it to deal with a fluid 
in itself independent, but upon which the great mass of 
tissues more or less depend. The greater number of the 
humoro-pathological doctrines are based upon the sup- 
position, that certain changes which have taken place in 
the blood are more or less persistent ; -and just in the 
very instance where these doctrines have practically ex- 
ercised the greatest influence, in the theory, namely, of 
chronic dyscrasiz, it is usually conceived that the change 
is continuous, and that by inheritance peculiar altera- 
tions in the blood may be transmitted from generation 
to generation, and be perpetuated. 

This is, I think, the fundamental mistake of the humo- 
ralists, the real hinge upon which their errors turn. Not 
that I doubt at all that a change in the composition of 
the blood may pertinaciously continue, or that it may 
propagate itself from generation to generation, but I do 
not believe that it can be propagated zm the blood itself 
and there persist, and that the blood is the real seat of 
the dyscrasia. 

My cellulo-pathological views differ from the humoro- 
pathological ones essentially in this, that I do not regard 
the blood as a permanent tissue, in itself independent, 
regenerating and propagating itself out of itself, but as 
in a state of constant dependence upon other parts. We 
need only apply the same conclusions which are univer- 
sally admitted to be true as regards the dependence of 
the blood upon the absorption of new nutritive matters 
from the stomach, to the tissues of the body themselves 
also. When the drunkard’s dyscrasia is spoken of, no- 
body of course imagines that every one who has once 
been drunk labours under a permanent alcoholic dyscra- 
sia, but the common opinion is, that, when continually 
fresh quantities of alcohol are ingested, continually fresh 


THEORY OF DYSCRASIA—ITS LOCAL ORIGIN. 163 


changes also declare themselves in the blood, so that its 
altered state must continue as long as the supply of fresh 
noxious matters takes place, or as, in consequence of 
a previous supply, individual organs remain in a diseased 
condition. If no more alcohol be ingested, if the organs 
which had been injured by the previous indulgence in it 
be restored to their normal condition, there is no doubt 
but that the dyscrasia will therewith terminate. This ex- 
ample, applied to the history of all the remaining dyscra- 
siz, elucidates in a very simple manner the proposition, 
that every dyscrasia is dependent upon a permanent supply 
of noxious ingredients from certain sources. As a con- 
tinual ingestion of injurious articles of food is capable of 
producing a permanently faulty composition of the blood, 
in like manner persistent disease in a definite organ is 
able to furnish the blood with a continual supply of mor- 
bid materials. 

The essential point, therefore, is to search for the 
local origins of the different dyscrasiz, to discover the - 
definite tissues or organs from which this derangement 
in the constitution of the blood proceeds. Now I am quite 
willing to confess that it has not in many cases hitherto 
been possible to find out these tissues or organs. In 
many cases, however, success has been obtained, although | 
it cannot be said in every instance in what way the blood | 
has become changed. Thus we have that remarkable 
condition, which may very well be referred to a dyscra- 
sia, the scorbutic condition, purpura, and the petechial 
dyscrasia. In vain will you look around for decisive in- 
formation as to the nature of this dyscrasia, and as to the 
kind of change experienced by the blood when purpura 
or scurvy show themselves. What has been found by 
one has, been contradicted by another, and it has even 
been shown that sometimes no change had taken place 
in the proportions of the grosser constituents of the 


164 LECTURE VI. 


blood. There remains in this case, therefore, a quid ig- 
notum, and you will, I am sure, deem it excusable, if we 
are unable to say whence a dyscrasia proceeds, of which 
we are altogether unacquainted with the nature. How- 
ever, the knowledge of the nature of the change in the 
blood does not involve an insight into the requisite con- | 
ditions for the dyscrasia, and just as little is the reverse 
the case. In the case of the hemorrhagic diathesis, also, 
it must at all events be regarded as an important step in 
advance, that we are in a number of instances able to 
point to a definite organ as its source, as, for example, 
to the spleen or liver. The chief point now is to deter- 
mine what influence the spleen or the liver exercises 
upon the special composition of the blood. If we were 
acquainted with the nature of the changes effected in the 
blood by the influence of these organs, it might not 
perhaps be difficult from our knowledge of the dis- 
eased organ also at once to infer what kind of change 
- the blood would experience. But it is nevertheless an 
important fact that we have got beyond the mere study 
of the changes in the blood, and have been able to ascer- 
tain that there are definite organs in which the dyscrasia 
has its root. 

In conformity herewith we must conclude that, if 
there is a syphilitic dyscrasia in which a virulent sub- 
stance circulates in the blood, this cannot be perma- 
nently present there, but that its existence must be due 
to the persistence of local depots (Heerde), whence new 
quantities of noxious matter are continually being intro- 
duced into the blood. By following this track we arrive 
at the conclusion which we have already mentioned, and 
which is of extreme importance in a practical point of 
view, that, namely, every permanent change which takes 
place in the condition of the circulating juices, must be 
derived from definite points in the body, from individual 


LOCAL ORIGIN OF DYSCRASIA. 165 


organs or tissues ; and this fact, moreover, is educed, 
that certain organs and tissues exercise a more marked 
influence upon the composition of the blood than others ; 
that some bear a necessary relation to this fluid, others 


only an accidental one. 


A Beid Sb Oe 8 Bal GI ead eb aeee es Bal 


MARCH 6, 1858. 
THE BLOOD. 


Fibrine—Its fibrille—Compared with mucus, and connective tissue—Homogeneous 
condition. 

Red blood-corpuscles—Their nucleus and contents—Changes of form—Blood-crys- 
tals (Hzeematoidine, Hemine, Hematocrystalline). 

Colourless blood-corpuscles—N umerical proportion—Structure—Compared with pus- 
corpuscles—Their viscosity and agglutination—Specific gravity—Crusta granu- 
losa—Diagnosis between pus-, and colourless blood-corpuscles. 


I inTEND to lay before you to-day, gentlemen, some 
further particulars with regard to the history of the blood. 

I concluded my last lecture by impressing upon you 
the necessity of localizing the different dyscrasiz ; em- 
ploying the term localize, not in its ordinary sense, as 
the dyscrasize have heretofore been considered as _ local- 
ized, but rather in a genetical meaning, in accordance 
with which we constantly refer the dyscrasiz to a pre- 
existing local affection, and regard some one tissue as 
the source of the persistent changes in the blood. 

If now we consider the different dyscrasize with regard 
to their importance and their source, two great categories 
of dyscrasic conditions may at the very outset be distin- 
guished, according namely as the morphological elements 
of the blood become changed, or the deviation is more 
of a chemical one, and seated in the fluid constituents. 


Among these latter, it is the fibrine, which, in conse- 
166 


‘ FIBRINE. 167 


quence of its coagulability, first, and that very soon 
after the blood has been removed from the living body, 
assumes a visible form, and which for this reason has 
frequently ‘passed for a morphological constituent of 
the blood. This notion concerning it has of late been 
maintained in many quarters, and has indeed always had 
a traditional existence in medicine, inasmuch as from 
ancient times fibrine was constantly brought forward in 
addition to the red constituents of the blood as a special 
element, and it was the custom to estimate the quality 
of the blood, not only from the number of the blood- 
corpuscles, but frequently in a much more positive man- 
ner from the amount of fibrine. 

This dissociation of fibrine from the other fluid consti- 
tuents of the blood is, to a certain extent, of real value, 
because fibrine, like the blood-corpuscles, is quite a 
peculiar substance, and so exclusively confined to the 
blood and the most closely allied juices, that it really 
may be viewed as connected rather with the blood-cor- 
puscles than with the mere fluids which circulate as 
serum. If we consider the blood in its really specific 
constituents, in those, by means of which it becomes 
blood, and is distinguished from other fluids, it cannot 
be denied that, on the one hand, the corpuscles with 
their hematine, and, on the other, the fibrine of the 
liquor sanguinis are the elements in which the specific 
differences must be sought for. 

If now we next proceed to consider these constituents 
a little more closely, the morphological description of 
fibrine is comparatively rapidly made. On examining 
it, as it appears in blood-coagula, it is nearly always 
found in the form described by Malpighi, the fibrillar. 
Its fibres generally form extremely fine interlacements, 
delicate networks, in which they usually cross and join 
one another in a somewhat tortuous form. The greatest 


168 LECTURE VII. 


variations exhibited by these fibres when forming out of 
the blood have reference to their size and breadth ; 
these are peculiarities con- 
cerning which it has not 
hitherto been possible to form 
any certain judgment. I meet 
with these variations pretty 
frequently, but without being 
in a position to assign the causes which determine them. 
The extremely fine and delicate fibres are those usually 
met with; but sometimes we find far broader, and 
almost ribbon-like fibres, which are much smoother, but 
in other respects, cross and interlace in pretty nearly 
the same manner. KHssentially, therefore, there is always 
present in a clot a network composed of fibres, in the 
meshes of which the blood-corpuscles are enclosed. If 
a drop of blood be allowed to coagulate, fine filaments 
of fibrine can be seen everywhere shooting up between 
the blood-corpuscles. 

With regard to the nature of these fibres, we may 
observe that there are only two other kinds which, his- 
tologically speaking, bear at all a near resemblance to 
them. The one kind occurs in a substance which, 
singularly enough, effects an approximation between the 
most ancient, perfectly antique, craseological ideas and 
the modern ones, namely in mucus. In the old Hippo- 
cratical system of medicine the whole mass of fibrine is, 
as is well known, included under the terms phlegma, 
mucus, and when we compare mucus with fibrine, we 
are obliged to confess that there does indeed exist a 
great similarity between them in the form they assume 
upon coagulation. In a similar manner to fibrine, 





Fig. 50. Coagulated fibrine from human blood. a, Fine, 6, coarser and broader 
fibrils. c, Red and colourless blood-corpuscles enclosed in the coagulum. 280 
diameters. 


FIBRINE, MUCUS AND CONNECTIVE TISSUE, 169 


mucus also forms into fibres, which frequently become 
isolated and then coalesce, so as to give rise to certain 
figures.. The other substance which belongs here is the 
intercellular, or, if you will, the gelatine-yielding sub- 
stance of connective tissue, the collagen (gluten of earlier 
writers). The fibrils of connective tissue only differ in 
that they are not usually reticulated, but run a parallel 
course, whilst in other respects they resemble those of 
fibrine in a high degree. The intercellular substance of 
connective tissue presents another point of resemblance 
with fibrine in the great analogy of its behaviour with 
reagents. When we expose it to the action of diluted 
acids, especially the ordinary vegetable acids, or also 
weak mineral acids, the fibres swell up and disappear 
before our eyes, so that we are no longer able to say 
where they are. The mass swells up, every interspace 
disappears, and it looks as if the whole were composed 
of a perfectly homogeneous substance. If we slowly 
wash it and again remove the acid, a fibrous tissue may, 
if the action have not been too violent, once more be © 
obtained, after which the previous condition can be pro- 
duced afresh, and changed again at pleasure. This 
behaviour has hitherto remained unexplained, and for 
this very reason Reichert’s view, which I have already 
mentioned, that the substance of connective tissue, is 
really homogeneous and the fibres are only an artificial 
product, or an optical delusion, has something alluring 
in it. In fibrine, however, the individual fibres can, 
much more distinctly than is the case with connective 
tissue, be so completely isolated, that I cannot help 
saying that I regard the separation into single fibres as 
really taking place, and not merely as an artificial one, 
or as a delusion on the part of the observer. 

But itis very interesting to observe that this fibrillar 
stage of fibrine is invariably preceded by a homogeneous 


170 LECTURE VII. 


one, just as connective tissue originally wears the form 
of a homogeneous intercellular substance (mucus) from 
which fibres are only by degrees, if I may so express 
myself, excreted, or, to employ the usual term, differen- 
tiated. So fibrine, too, which is first of all gelatinous, 
becomes differentiated into a fibrillar mass. And indeed 
in the case of inorganic substances also we find certain 
analogous appearances. From deposits of calcareous 
salts or silicic acid, which were originally perfectly gela- 
tinous and amorphous, solid granules and crystals are 
gradually separated. 

The name fibrils may therefore still be retained to 
designate the usual form in which fibrine presents itself, 
but at the same time it must be borne in mind, that this 
substance originally existed in a homogeneous, amor- 
phous, gelatinous condition, and can again be reduced 
to it. This reduction can not only be effected artificially, 
but takes place also naturally in the body itself, so that 
where we have previously found fibrils, we may after- 
wards meet with the fibrine in a homogeneous condi- 
tion, as, for example, in the vessels, where aneurysmal 
coagula, and others, are gradually converted into a 
homogeneous mass of cartilaginous density. 


Now, with reference to the second portion of the 
blood, the dlood-corpuscles, I may express myself briefly, 
as they are well-known elements. I have already 
remarked that nearly all the histologists of the present 

meee time are agreed that the co- 

a , ‘ loured corpuscles of the blood 
® © os a@r of man and the higher mam- 

og © maha contain no nuclei, but 
that they are simple vesicles, 


Fig. 51. Nucleated blood-corpuscles from a human foetus, six weeks old. 
a. Homogeneous cells varying in size, with simple, relatively large nuclei, of which 


RED BLOOD-CORPUSCLES AND THEIR CONTENTS. 171 


concerning the cellular nature cf which doubts might 
be permitted, if we did not happen to know that, at 
certain periods of the development of the embryo, they 
do contain nuclei. An ordinary red blood-corpuscle must 
therefore be considered as composed of a closed mem- 
brane, containing a tolerably tough mass, which is the 
seat of the colour. Now, in man the blood-corpuscles 
are, as is well known, flat, disc- or plate- > 


Fia. 52, 
shaped bodies, with a central depression wa Ig 
h Bicwh tar: @ 6033 
on each surface, and, when regular in e 
Rites m ,9%S 
form, constitute, as it were, a ring, in the d¢ 39 
centre of which the colour is fainter from : 


the diminished thickness. The contents are generally 
somewhat summarily regarded as consisting of hema- 
tine, or the colouring matter of the blood. They are, 
however, unquestionably very complex, and what is 
called hematine forms merely a part of them ; how great 
a part it has not been hitherto possible to determine. 
Whatever other matters are contained within the blood- 
corpuscle belong entirely to its chemistry. Certain 
changes produced by the action of external media con- 
stitute all that can be seen of them. We observe that 
the blood-corpuscles, according as they imbibe oxygen, 
or contain carbonic acid, appear light or dark, whilst 
they alter their form a little. We know, further, that 


a few are slightly granular, but the greater number more homogeneous; at * a 
colourless corpuscle. 6. Cells with extremely small, but well defined nuclei, and 
distinctly red contents. c. After the addition of acetic acid the nuclei are seen in 
some instances shrivelled and jagged, in several, double; at * a granular corpuscle. 
280 diameters. 


Fig. 52. Human blood-corpuscles from an adult. a, An ordinary dise-shaped, 
red blood-corpuscle; 6, a colourless one; c, red corpuscles seen in profile, and 
standing upon their rims. d. Red corpuscles arranged in the form of rouleaux of 
money. ¢. Red corpuscles which have become irregular in outline, and shrivelled 
through loss of water (exosmosis). /. Shrivelled red corpuscles, with tuberculated 
margins, and a projection, like that produced by a nucleus, upon the flat surface of 
the disc. g. A still more shrivelled state. A. The highest degree of shrivelling 
(melanic corpuscles), Magnified 280 diameters. 


172 LECTURE VII. 


by the action of chemical fluids, certain quantities of 
water are abstracted from the corpuscles, and that they 
then shrivel up and experience peculiar changes in form, 
which might very easily give rise to errors. These are 
not unimportant conditions, and I will therefore now add 
a few words concerning them. 

When a blood-corpuscle is exposed to a loss of water 
by the action of a strongly concentrated liquid upon it, 
the first thing we observe is that, as fast as fluid exudes, 
little prominences arise on the surface of the corpuscle, 
at first very much scattered, sometimes at the border, 
sometimes more towards the middle, and in the latter 
case, occasionally bearing a deceptive resemblance to a 
nucleus (Fig. 52, e, f). This has been the source of the 
erroneous assumption of nuclei, which have been so 
much described. If a blood-corpuscle be watched for a 
considerable time whilst under the action of concentrated 
media, more and more protuberances are seen to arise, 
and the surface of the corpuscle becomes less in diameter. 
At the same time, little folds and knobs form with con- 
tinually increasing distinctness on the surface, and the 
cell becomes jagged, stellate, and angular (Fig. 52, g). 
Jagged bodies of this sort are to be seen every moment 
on examining blood which has been for some time ex- 
posed to the air. Hven mere evaporation will produce 
this change. We can effect it with great rapidity by 
altering the composition of the serum by the addition of 
salt or sugar. If the abstraction of water continue, the 
corpuscle grows smaller still, and ultimately becomes 
smooth again, and at the same time globular (Fig. 52, h), 
or even perfectly spherical, whilst its colour appears 
much more intense, and the contained mass assumes 
quite a deep blackish-red hue. Hence we are able to 
draw the not uninteresting conclusion, that this exos- 
mosis consists essentially in a withdrawal of water, dur- 


EFFECTS OF FLUIDS UPON THE RED CORPUSCLES. 173 


ing which perhaps one or more other matters pass out, 
as, for example, salt, but the essential constituents 
remain behind. The hzmatine does not follow the 
water ; the membrane of the blood-corpuscles keeps it 
back, so that when a large quantity of fluid is lost, the 
heematine in the interior must of course become propor- 
tionately increased in density. 

_ The reverse is the case when we employ diluted fluids. 
The more diluted the fluid, the more does the blood-cor- 
puscles enlarge; it swells up and becomes paler. On 
treating blood-corpuscles, which have become smaller 
from the action of concentrated fluids, with water, we 
see them pass back from the globular into the angular 
form, and from this into the discoidal one ; after which 
they continually become more and more globular, often 
assume very peculiar shapes, and again grow paler. 
This process may, if the dilution’of the blood be effected 
with great precaution, be continued until the blood-cor- 
puscles scarcely seem to retain a trace of colour, though 
they still remain visible. In ordinary cases, when much 
liquid is added at once, such a violent revolution is pro- 
duced in the economy of the blood-corpuscle, that an 
escape of the hematine immediately ensues. We then 
obtain a red solution, in which the colouring matter is 
free and dissolved in the fluid. I call your attention to 
this peculiarity, because it is continually occurring in the 
course of investigations, and because it explains one of 
the most important phenomena in the formation of 
pathological deposits of pigment, in which we meet with 
a precisely similar escape of heematine from the blood- 
corpuscles (Fig. 54, a). The expression generally made 
use of under such circumstances is, that the blood- 
corpuscles are dissolved, but it has long been a well- 
known fact that, as was first shown by Carl Heinrich 
Schultz, although there apparently no longer exist any 


174 LECTURE VIL 


cells, yet their membranes may, by means of an aqueous 
solution of iodine, again be rendered visible, whence it 
is evident that it was only the high degree of distension 
and the extraordinary thinness of the membranes which 
prevented the corpuscles from being seen. Indeed, very 
violent action on the part of substances chemically dif- 
ferent is required, in order to effect a real destruction of 
the blood-corpuscles. If, immediately after they have 
been treated with a very concentrated solution of salt, 
water be added in large quantity, we may succeed in 
bringing things to such a pass that the contents of the 
corpuscles are abstracted without their swelling up, and 
their membranes remain behind visible. This was the 
reason why Denis and Lecanu asserted that the blood- 
corpuscles contained fibrine ; for they believed that, by 
treating them first with salt and then with water, they 
were able to demonstrate its presence in them. This so- 
called fibrine is, however, as I have shown, nothing more 
than the membranes of the blood-corpuscles ; real fibrine is 
not contained in them, although their walls are certainly 
composed of a substance which has more or less affinity 
to albuminous matters, and may, when obtained in 
large masses, present appearances reminding one of 
fibrine. 

Now with regard to the substances contained in the 
blood-corpuscles, they happen quite recently to have 
become invested with great interest in consequence of 
the more morphological products which have been 
observed to arise out of them, and which have produced 
a kind of revolution in the whole theory of the nature of 
organic matters. I refer here to the peculiar forms of 
coloured crystals, which can, under certain circumstances, 
be obtained from the colouring matter of the blood, and 
which have acquired not only on their own account great 
chemical, but also very considerable practical, interest. 


HASMATOIDINE. 175 


We have already become acquainted with three different 
kinds of crystals, of which hematine seems to be the 
common origin. 

To the first form, with which I at one time busied 
myself much, I have given the name of Hematordine. 
This is one of the most frequent of metamorphic products, 
and is spontaneously formed in the body out of haema- 
tine, and that indeed often in such large quantities that 
its excretion can be perceived with the naked eye. This 
substance in its perfect form presents itself in the shape 
of oblique rhombic columns, and is of a beatiful yellow- 
ish-red, or frequently, when in thicker pieces, deep ruby- 
red, colour, and forms one of the most beauti- 
ful crystals we are acquainted with. In little 
plates too it is not uncommonly met with, and & A 
frequently bears a considerable resemblance 8 =| 
to the crystalline forms of uric acid. In the 
majority of cases the crystals are very small, | 
not merely microscopical, but even somewhat difficult of 
observation with the microscope. A man must either be 
a very keen observer, or provided with special prepara- 
tory knowledge, else he will frequently discover in the 
spots where the hematoidine is lying nothing more 
than little streaks, or an apparently shapeless mass. 
But, upon more accurate inspection, the streaks resolve 
themselves into minute rhombic columns, the mass into 
an aggregation of crystals. This substance may be con- 
sidered as the regular, typical, ultimate form into which 
hematine is converted in any part of the body where 
large masses of blood continue to lie for any length of 
time. An apoplectic effusion in the brain, for example, 
cannot be repaired by any other process than by a large 
portion of the blood undergoing this form of crystalliza- 


Fig. 538. 





Fig. 58. Crystals of Hematoidine in different forms (Comp. ‘ Archiv. f. path. 
Anat.,’ vol. i, p. 391, plate iii, fig. 11). Magnified 300 diameters. 


176 LECTURE VII. 


tion, and if we afterwards find a coloured cicatrix at the 
spot, we may feel perfectly assured that the colour is 
dependent upon the presence of hematoidine. When 
a young woman menstruates, and the cavity of the 
Graafian vesicle, from which the ovum has been ex-— 
truded, becomes filled with coagulated blood, the hema- 
tine is gradually converted into hematoidine, and we 
afterwards find at the spot where the ovum had lain, the 
beautiful deep-red colour of the hematoidine crystals, 
which remain as the last memorials of this episode. In 
this manner we can count the number of apoplectic 
attacks, or calculate how often a young girl has menstru- 
ated. Every extravasation may leave behind its little con- 
tingent of hematoidine crystals, and these, once formed, 





remain in the interior of the organ, in the shape of 
compact bodies endowed with the greatest powers of 
resistance. 

With respect to the peculiarities of heematoidine, it has, 
in a theoretical point of view, another special claim to 


Fig. 54. Pigment from an apoplectic cicatrix in the brain (‘ Archiv,’ vol. i, pp. 
401, 454, plate iii, fig. 7). a. Blood-corpuscles which have become granular and 
are in process of decolorization. 6. Cells from the neuroglia, some of them pro- 
vided with granular and crystalline pigment. c. Pigment-granules. d. Crystals of 
Hematoidine. /. Obliterated vessel with its former channel filled with granular and 
crystalline red pigment, 300 diameters. 


HIMINE. 177 


our interest, from its-presenting to us a series of proper- 
ties, which render it conspicuous as the only substance in 
the body, at least, that we are as yet acquainted with, 
which is allied to the colouring matter of the bile (Chole- 
pyrrhine).. By the direct action of mineral acids, or after 
previous treatment and preparation by means of alkalies, 
the same, or precisely similar, colour-tests are obtained, 
which are yielded by the colouring matter of the bile 
when treated with mineral acids, and it seems also from 
other facts, that we have here a body before us, which is 
very intimately connected with the colouring matter of 
the bile. This circumstance derives its especial interest 
from its being supposed, for other reasons also, that the 
coloured constituents of the bile are products of the de- 
composition of the red colouring matter of the blood. 
In the interior of extravasations there really does arise a 
yellowish red substance which may be designated as a 
newly formed kind of biliary colouring matter. | 
The second kind of crystals which arise out of hema- 
tine was discovered later ; they are very similar to the 
preceding ones, but differ from them in that they do not 
occur as a spontaneous product in the body, but must be 
artificially produced. They are more of a dark brownish 
Fie. 55. 


Olt wy’ 


eG - 74 


colour and usually form flat rhombic plates with more 
acute angles ; they are in an extraordinary degree capa- 
ble of resisting tests, and also do not, when acted upon 





Fig. 55. Crystals of Hxmine, artificially procured from human blood. 300 dia- 
meters. 


12 


178 LECTURE VII. 


by the mineral acids, exhibit the peculiar play of colours 
afforded by hematoidine. This second kind of crystals 
has received the name of Hemuine from their discoverer 
Teichmann. Quite recently Teichmann has himself be- 
gun to entertain doubts as to whether it is not really a 
sort of hamatine. These forms do not present as yet 
the slightest pathological interest, but, on the other hand, 
they have proved of very great importance in forensic 
medicine on account of their having been recently em- 
ployed as one of the surest tests for the examination of 
blood-stains. I myself have been in a position to make 
experiments of this sort in forensic cases. For this pur- 
pose the best mode of proceeding is to mix dried blood in 
as compact a form as possible with dry, crystallized, 
powdered common salt, and then to add to this mixture 
glacial acetic acid, and evaporate at a boiling heat. 
When this has been done, crystals of hemine are found 
where the blood-corpuscles or the substance previously 
lay, in which the presence of hematine was doubtful. 
This is a reaction which must be ranked among the most 
certain and reliable ones with which we are acquainted. 
There is no other substance in which we know such a 
transformation to take place, but hematine. This test 
is extremely important, because it is applicable in the 
case of extremely minute quantities, only they must not 
be spread over too large a surface. It would therefore 
not be easy of application in a case where we had to deal 
with a cloth which had been dipped into a thin, watery, 
fluid coloured with blood. Yet I was able, in the case 
of a murdered man, on the sleeve of whose coat blood 
had spurted, and where some of the drops were only a 
line in diameter, from these minute specks to produce 
innumerable crystals of heemine, though of course micro- 
scopical ones. In cases in which the ordinary chemical 
tests would necessarily absolutely fail on account of the 


i Mee waiter, Gt aia ae 


HAMATO-OCRYSTALLINE, 179 


smallness of the quantity, we are still able to obtain 
hemine. When the massof blood is so very small, the size 
of the crystals is certainly also extremely minute, and we 
then find, asin the case of heematoidine, small needles of 
an intensely brown colour and provided with acute angles. 

The third substance which belongs to this series, is the 
so-called Hemato-crystalline, a substance about the dis- 
covery of which the learned still dispute, for the simple 
reason that it was found out piecemeal. The first obser- 
vation concerning it was made by Reichert in extrava- 
sations in the uterus of the guinea-pig, in a preparation 
which, I think, had already laip for some little time in 
spirits. . This observation of his acquired especial signifi- 
cance because he showed that these crystals in certain 
respects behaved like organic substances, inasmuch as 
they became larger through the action of certain agencies, 
and smaller through that of others, without any change 
of form, a phenomenon which, up to that time, had not 
been known to take place in crystals. Afterwards these 
crystals were again discovered by Kolliker, but Funke, 
Kunde, and especially Lehmann, have examined them 
more closely. The result has been that they are very 
different in different classes of animals, but hitherto it has 
not been possible to discover any definite reason for their 
existence, or to obtain any insight into the nature of the 
substance itself. In man the crystals are tolerably large. 
At first it was believed that they only occurred in the 
blood of certain organs, but it has since turned out that 
they occur everywhere, though they are obtained with 
greater readiness in certain morbid conditions. In a few 
very rare cases it happens that they are found already 
formed in the blood of the dead bodies of animals. These 


crystals are very easily destructible ; both when they dry. 


up and when they become moist, or are brought into 
contact with any fluid medium, they perish, and they are 


rapa 


180 LECTURE VII. 


therefore only observed in certain transitional stages, 
which must be exactly hit upon, in the destruction of 
blood-corpuscles. The well-developed forms in man are 
perfectly rectangular bodies ; but very frequently they 
are extremely small, and nothing is seen but simple 
spicules which shoot up into the object at certain spots 
in large masses. There is besides this peculiarity about 
them, that they retain the property which hematine 
itself has of becoming bright red with oxygen and dark 
red with carbonic acid. It is still, however, a frequent 
subject of discussion whether their whole substance is 
composed of colouring matter, or whether in this case 
also the crystals are really colourless and merely impreg- 
nated with pigment ; this much, however, may be regarded 
as certain, that the colour has something very character- 
istic about it, and that the existence of a close connec- 
tion between it and the ordinary colouring matter of the 
blood cannot be doubted. 

If we now revert to the natural morphological ele- 
ments of the blood, we meet with the colourless corpus- 
cles as its third constituent. They are present in compa- 
ratively small quantity in the blood of a healthy man. 
To three hundred red corpuscles we reckon about one 
colourless one. As they generally present themselves in 
the blood, they are spherical corpuscles, which are some- 
times a little larger, sometimes a little smaller than, or 

of the same size as, ordinary 





oe red blood-corpuscles, from which 

‘oe ook ea CW® they are, however, strikingly 
12 @6 ©@ 550 distinguished by the want of all 
& eq “ colour and by their perfectly 


@ 
spherical form. 


In a drop of blood which has become quiet, the red cor- 


Fig. 56. Colourless blood-corpuscles from a vein of the pia-mater of a lunatic. 
A. Examined when fresh ; a in their natural fluid, 6 in water. 3B. After the addi- 


COLOURLESS BLOOD-CORPUSCLES, 181 


puscles are usually found aggregated in rows, presenting 
the familiar form of rouleaux of money, with their flat 
discs one against the other (Fig. 52, d) ; in the interspaces 
may be observed here and there one of these pale, spheri- 
cal bodies, in which in the first instance, when the blood is 
quite fresh, nothing more can be distinguished than an 
occasionally slightly granular-looking surface. If water 
be added, the colourless corpuscles are seen to swell up, and 
in proportion as they absorb the water, a membrane first 
becomes distinct ; then granular contents gradually come 
into view with more and more clearness, and at last some 
indication is perceived of the presence of one or several 
nuclei. The apparently homogeneous globule is gradu- 
ally transformed into a structure with delicate walls, and 
often so fragile, that when water is incautiously added, 
the external parts begin to fall to pieces, and in the in- 
terior a somewhat granular mass displays itself, which 
becomes looser and looser, and discloses within it a nu- 
cleus generally in process of division, or several nuclei. 
These may be made to display themselves with much 
greater rapidity, by treating the object with acetic acid, 
which renders the membrane translucent, dissolves the 
nebulous contents, and causes the nucleus to coagulate 
and shrivel up. The nuclei then are seen to be dark bo- 
dies with sharply defined outlines, and one or more in 
number according to circumstances. In short, we ob- 
tain in this way in the majority of cases the view of an 
object which presents the peculiar appearance that one 
of our confreres now present, Dr. Giiterbock, first pro- 
claimed to be the special characteristic of pus-corpuscles. 
The question concerning the resemblance or want of re- 


tion of acetic acid: a—e, cells with a single, granular nucleus, which becomes pro- 
gressively larger§ and is finally provided with a nucleolus. d. Simple division of the 
nuclei, e¢. A more advanced stage of the division. /—h. Gradual division of the 
nuclei into three parts. «t—. Four and more nuclei, 280 diameters. 


182 LECTURE VII. 


semblance between the colourless cells of the blood and 
pus-corpuscles still continues to occupy the attention of 
observers, and it will probably still require a number of 
years before the views entertained with regard to the 
connection between the colourless corpuscles and pyzemia 
have been rendered so clear that relapses on one side 
or the other will not now and then recur. There is 
namely this source of error, that upon examining a num- 
ber of persons, in the blood of several among them cor- 
puscles will be found which have only a single nucleus, 
and that a very large one and not unfrequently provided 
with a nucleolus, whilst in the blood of others no corpus- 
cles will be seen which do not contain several nuclei. 
Now, since these latter bear a great resemblance to pus- 
corpuscles, those observers, who had previously chanced 
to meet with nothing but uni-nuclear corpuscles in nor- 
mal blood, cannot be blamed for believing, in another 
case in which they see multi-nuclear ones, that they have 
something essentially different before them, namely, pus- 
corpuscles in the blood, and that the case is one of pyx- 
mia. But, strange to say, the corpuscles with one nu- 
cleus form the exception, and you may look for a long 
time without finding blood in which all the cells have 
only one nucleus. Oddly enough to-day, while occu- 
pied in preparing the microscopical objects, I stumbled 
upon a specimen of blood, in which scarcely 
: anything but cells with one nucleus are to be 
OS © met with, and these in extremely large num- 
beh ber ; it was taken from a man who died of 
smallpox, and in whom a very highly remark- 

able acute hyperplasia of the bronchial glands existed. 
Now, one might be inclined to believe that these are 


Fie. 57. 


e 
Fig. 57. Colourless blood-corpuscles in variolous leucocytosis. a. Free or naked 
nuclei. 5, b. Colourless cells with small, simple nuclei. c¢. Larger, colourless cells, 
with large nuclei and nucleoli. 300 diameters. 


PROPERTIES OF COLOURLESS BLOOD-CORPUSCLES. 183 


different qualities of blood. But in opposition to such 
an idea it must be remarked, that, although in the cases 
in which the one or the other kind of corpuscles exist in 
large quantities, we have to deal with a pathological phe- 
nomenon, yet that, when we do not find such large 
quantities, we have before us only an earlier or a later 
stage of the development of the elements. For one and 
the same blood-corpuscle may, in the course of its life, 
have one or several nuclei, the one belonging to an 
earlier, the several to a later, stage of its existence. 
You must always bear in mind, that the change is seen 
to take place in the same individual in a short time, in- 
deed often in the course of a few hours, so that in blood 
which had previously only contained one sort, after- 
wards quite a different one may be found—a proof of the 
rapidity of the change to which these bodies are sub- 
jected. 

Allow me, gentlemen, to add a few words with regard 
. to the more palpable relations which the individual con- 
stituents of the blood present towards one another. It 
is, as you well know, generally assumed that of the mor- 
phological constituents only two are accessible to the 
grosser perception of the naked eye, namely, the red 
corpuscles in the clot, and the masses of fibrine, which 
under certain circumstances form a buffy coat, but that, 
on the other hand, the colourless cells are not to be per- 
ceived by the unaided sight. This is a notion which I 
consider myself bound to correct. The colourless cor- 
_puscles, whenever they are present in considerable num- 
bers, become very distinctly manifest to the more prac- 
tised eye during the separation of the constituents of the 
blood, and especially when the coagulation is accompanied 
by movement; and they then exhibit a peculiarity, 
with which it is as well that one should be acquainted 
when one is required to pass judgment upon specimens de- 


184 LECTURE VII. 


rived from post-mortem examinations, and the ignorance 
of which has led to great errors. The colourless cor- 
puscles possess namely, as was brought to light in the 
discussion which Herr Ascherson, now here present, had 
some time ago with E. H. Weber, the peculiar property 
of being sticky, so that they 
readily adhere to one another, 
and under certain circumstances 
also cling fast to other parts, 
when the red corpuscles do not 
present this phenomenon. This 
tendency to adhere to other 
parts is particularly evident 
when several of the corpuscles 


Fig. 58. 





are at the same time placed in a position which enables 
them to stick together. Thus, in blood in which 
there is an actual increase in the number of colourless 
cells, it is extremely common for agglutinations to take 
place among them, as soon as the pressure, under which 
the blood flows, is diminished ; in every vessel, in which 
the stream becomes slower, and the pressure weaker, 
an agglutination of the corpuscles may take place. 

The adhesiveness (viscosity) of the colourless blood- 
corpuscles produces besides this effect, that, as has been 
shown by Herr Ascherson, when the blood is flowing as 
usual through the capillary vessels, the colourless cor- 
puscles generally float rather more slowly than the red, 
and that, whilst these move along more in the centre of 
the vessel in a continuous stream, a comparatively large 
vacuity 1s left at the circumference, within which the 


Fig. 58. A. Fibrine clot from the pulmonary artery, and corresponding to its 
terminal branches; at a, a beset with largish patches, composed of heaps of white 
cells; at 6, b, b with specks of an analogous nature. Natural size. 

B. A portion of one of these specks or heaps, composed of thickly crowded, 
colourless blood-corpuscles. Magnified 280 diameters. 


AGGLUTINATION OF COLOURLESS BLOOD-CORPUSCLES. 185 


colourless corpuscles’ move, and that indeed often with 
such constancy, that Weber came to the conclusion that 
every capillary lay within a lymphatic vessel, in the inside 
of which the colourless blood- or lymph-corpuscles 
floated. But there cannot be the least doubt but that 
the canals in question are single ones, in which 
the colourless corpuscles float along closer to 
the walls than the red ones ; and it is in this 
peripheral space that, whilst the corpuscles 
move on, we see one here and there stick fast 
for a moment, then tear itself away and again 
move on slowly, so that the name of the s/ug- 
gish layer (triage Schicht), applied to this part 
of the stream, has been universally adopted. 

These two peculiarities, first, that, when the 
current becomes weaker, the corpuscles here and there 
cling to the walls of the vessel, and in some measure 
adhere to them, and, secondly, that they gather together 
and become conglomerated into largish masses, combine 
to produce this effect, that, when there exists a large 
number of colourless corpuscles in the blood, and death 
occurs, as it does in ordinary cases, after a gradual 
weakening of the propelling force, the colourless cor- 
puscles collect in vessels of every description, into small 
heaps, and generally lie upon the outside of the later 
formed blood-clot. 

If, for example, we pull out of the pulmonary artery 
the generally very tough clot of blood which fills it, 
minute granules will perchance be found upon its surface 
(Fig. 58, A), little beads of a white colour, which look 
like specks of pus, or are connected several of them toge- 
ther in the form of a string of pearls. This appearance 





Fig. 59. Capillary vessel from the web of a frog’s foot. 1. The central stream 
of red corpuscles. /, 7, /. The sluggish, peripheral layer of the stream with the 
colourless corpuscles. Magnified 280 diameters. 


186 LECTURE VII. 


most frequently presents itself at those points where the 
number of the bodies is normally the largest, namely in 
the interval between the orifice of the thoracic duct, and 
the capillaries of the lungs. The naked eye can with 
tolerable ease detect in these clots the greater or less 
quantity of colourless corpuscles. Under circumstances 
inducing the presence of a very large number of them, 
whole heaps of them may be seen, investing different 
parts of the coagulum like a sheath, and if one of these 
heaps be placed under the microscope, many thousands 
of colourless corpuscles are seen crowded together. 

If the coagulation of the blood takes place, when it is 
more at rest, another appearance is presented with great 
distinctness, as may be seen in the vessels used to receive 
the blood after veneesection. When the fibrine does not 
coagulate very quickly, as is the case in inflammatory 
blood, the blood-corpuscles begin, in consequence of 
their greater specific gravity, to sink through the fluid. 
This subsidence proceeds, as is well known, to such a 
pitch, that, after the fibrine has been removed by stir- 
ring, the serum becomes perfectly clear, in consequence 
of the corpuscles’ falling to the bottom. On defibrinating 
blood rich in colourless corpuscles, and allowing it to 
stand, a double sediment forms, a red and a white one. 
The red one constitutes the deeper, the white one the 
more superficial stratum, and the latter looks exactly as 
if a layer of pus were lying upon the blood. When the 
blood has not been deprived of its fibrine, yet coagulates 
slowly, the subsidence of the corpuscles does not take 
place so completely, but only the highest part of the 
liquor sanguinis becomes free from corpuscles ; and when 
after this the fibrine coagulates, we obtain the well-known 
crusta phlogistica, the buffy coat, and on looking for the 
colourless corpuscles, we find them forming a separate 
layer at the lower border of the buffy coat. This pecu- 


stereos eee 
aeeeepeeesee 


RED, WHITE AND COLOURLESS BLOOD-CORPUSCLES. 187 


liarity is simply explained by the different specific gravity 
of the two kinds of blood-corpuscles. The colourless 
ones are always light, poor in solid matter and very deli- 
cate in structure, whilst the red ones are as heavy as 
lead in comparison, owing to their richness in hzematine. 
They therefore reach the bottom 
with comparatively great rapidity, 
whilst the colourless ones are still 
engaged in falling. If two bodies of 
different specific gravities be allowed 
to fall from a sufficient height in the 
open air, the lighter one will, you 
know, in a similar manner, reach the 
ground after the other, owing to the 
resistance of the air. 

In the coagulation which takes 
place in blood derived from venesection, this white clot 
does not usually form a continuous, but an interrupted, 
layer, composed of little heaps or nodules adhering to the 
under side of the buffy coat. Hence Piorry, who was 
the first to observe this appearance, but completely mis- 
interpreted it, seeing that he referred it to an inflamma- 
tion of the blood itself (Heemitis) and established the 
doctrine of Pyzmia, upon it, termed this form of buffy 
coat crusta granulosa. It really consists of nothing more 
than large accumulations of colourless corpuscles. 

Under all circumstances this layer resembles pus in 
appearance, and since, as we have already seen, the 
colourless blood-cells individually are constituted like 
pus-corpuscles, you see that we are liable not only in the 
case of a healthy person to take colourless blood-cells for 

















Fig. 60. Diagram of a bleeding-glass with coagulated hyperinotic blood. a, The 
level of the liquor sanguinis. c. The cup-shaped buffy coat. 7. The layer of lymph 
(Cruor lymphaticus, Crusta granulosa), with the granular and mulberry-like accumu- 
lations of colourless corpuscles. +r. The red clot. 


188 LECTURE VII. 


pus-corpuscles, but still more so in pathological condi- 
tions when the blood or other parts are full of these ele- 
ments. You can imagine how apt the question is to 
present itself, which has already been seriously raised by 
Addison and Zimmermann, whether pus-corpuscles are 
not merely extravasated colourless blood-cells, or vice 
versa, whether the colourless blood-cells found within 
the vessels are not pus-corpuscles which have been ad- 
mitted into them from the exterior. We are here called 
upon for the first time to make the practical application 
of the principles which I laid down with regard to the 
specific nature and heterology of elements (p. 92.) <A 
pus-corpuscle can be distinguished from a colourless 
blood-cell by nothing else than its mode of origin. If 
you do not know whence it has come, you cannot say 
what it 1s; you may conceive the greatest doubt as to 
whether you are to regard a body of the kind as a pus- 
or a colourless blood-corpuscle. In every case of the 
sort the points to be considered are, where the body 
belongs to, and where its home is. If this prove to be 
external to the blood, you may safely conclude that it is 
pus; but if this is not the case, you have to do with 
blood-cells. 


Ls pheted teh de Han Ve Lakidg 


MARCH 10, 1858. 
BLOOD AND LYMPH. , 


Change and replacement of the constituents of the blood—/ibrine—Lymph and its 
coagulation—Lymphatic exudation—Fibrinogenous substance—Formation of 
the buffy coat—Lymphatic blood, hyperinosis, phlogistic crasis—Local forma- 
tion of fibrine—Transudation of fibrine—Formation of fibrine in the blood. 

Colourless blood-corpuscles (lymph-corpuscles)—Their increase in hyperinosis and 
hypinosis (Erysipelas, pseudo-erysipelas, typhoid fever)—Leucocytosis and 
leukeemia—Splenic and lymphatic leukemia. 

The spleen and lymphatic glands as blood-making organs—Structure of lymphatic 
glands. 


Tue last time, gentlemen, I introduced to your notice 
the individual morphological elements of the blood, and 
endeavored to portray their special peculiarities. Allow 
me to begin to-day with a few words concerning their 
origin. 

From the facts which have been ascertained with 
regard to the first development of the elements of the 
blood, important conclusions may be drawn respecting 
the nature of the changes which take place in the mass 
of the blood in deceased conditions. Formerly the blood 
was regarded more as a juice shut up by itself, which 
was indeed to a certain extent connected with the parts 
external to it, but yet was in itself endowed with real 


durability, and it was assumed that it could retain pecu- 
189 


190 LECTURE VIII. 


liar properties for lengthened periods, nay, that these 
might cling to it for many years. Of course it was im- 
possible at the same time to entertain the opinion, that 
the constituents of the blood were of a perishable nature, 
and that new elements were added to it, to replace the old 
ones. For the durability of a part as such presupposes 
either that all its individual particles are durable, or that 
these individual particles are continually producing fresh 
ones within the part which bear impressed upon them all 
the peculiarities of the old ones. In the case of the 
blood, therefore, one would have to assume that its con- 
stituents really did subsist for years, and could for years 
present the same changes, or one would have to imagine 
that the blood transmitted something from one particle 
to another, and that from a parent blood-cell to its pro- 
geny something hereditary was handed down. Of these 
possibilities the former has, I believe, at the present time 
been pretty generally discarded. No one, I think, now 
imagines that the individual constituents of the blood last 
on for years. On the other hand, the possibility that the 
corpuscles of the blood are renewed by propagation, 
and that certain peculiarities which are introduced into 
the blood at a certain time, are transmitted from cor- 
puscle to corpuscle, cannot straightway be rejected. 
But the only phenomena pointing to such a propagation 
of the blood, concerning which we possess any positive 
information, belong to an early period of embryonic life. 
There it appears from observations which were only the 
other day again confirmed by Remak, the existing blood- 
corpuscles undergo direct division, the process being that, 
in a corpuscle which during the early stages of its deve- 
lopment had displayed itself as a nucleated cell, first of 
all a partition of the nucleus takes place (Fig. 51, c) ; 
and that then the whole cell becomes constricted in the 
middle, and gradually is really seen to pass into a state 


ORIGIN OF BLOOD-CORPUSCLES—LYMPH. 191 


of complete division. At this early period it is therefore 
certainly allowable to regard a blood-corpuscle as en- 
dowed with qualities which are propagated from the first 
series of cells to the second, and from this to the third, 
and so on. ; 

In the blood of a fully developed human being, nay 
even in that of a foetus in the later months of pregnancy, 
these phenomena of partition are no longer known, and 
not a single one of the facts which can be adduced from 
the history of development speaks in favour of an increase 
of the cellular elements taking place in fully developed 
blood by means of direct division, or any other formative 
process taking its rise in the blood itself. As long as the 
possibility was regarded as demonstrated, that cells might 
arise out of simple cytoblastema by means of the direct 
precipitation of different substances, so long was it pos-" 
sible to conceive new precipitates as forming in the liquor | 
sanguinis from which cells were produced. But this 
view also has been abandoned. All the morphological © 
elements of the blood, whatever may be their nature, are 
at present considered to be derived from sources external 
to the blood. On all hands recourseris had to organs 
which do not communicate with the blood directly, but 
rather by the means of intermediate channels. The 
principal organs which here come into play are the 
lymphatic glands. Lymph is the fluid which, whilst it \ 
conveys certain substances to the blood which come from 
the tissues, at the same time brings along with it the 
corpuscular elements out of which the blood-cells con- 
tinually recruit their numbers. 

With regard to two of the constituents of the blood, 
there can, I think, be scarcely any doubt but that this is 
the view which is perfectly warranted, I mean with 
regard to the fibrine and the colourless corpuscles. As 
for the fibrine, the properties of which I brought to your 


199 LECTURE VIII. 


notice last time, it is a very essential and important fact 
that the fibrine which circulates in lymph differs in cer- 
tain respects from that contained in the blood, which we 
see on examining different extravasations, or blood drawn 
from a vein. The fibrine of lymph has this special pecu- 
liarity, that under ordinary circumstances it coagulates 
within the lymphatic vessel neither during life nor after 
death, whilst blood in many instances coagulates even 
during life, and regularly does so after death, so that 
coagulative power is attributed to blood as being one of 
its regular properties. In the lymphatics of a dead ani- 
mal or human corpse, no coagulated lymph is met with, 
yet the coagulation takes place directly the lymph is 
brought into contact with the air, or has changes imparted 
to it by some diseased organ. 

The explanation of this peculiarity has been attempted 
in very different ways. For my own part I must still 
adhere to the view that there is, properly speaking, no 
perfectly developed fibrine contained in lymph, but that 
it becomes perfect either by contact with the atmosphe- 
ric air, or in abnormal conditions by the introduction into 
it of altered matters. Normal lymph contains a substance 
which is very readily converted into fibrine, and is, when 
it has once coagulated, scarcely to be distinguished from 
fibrine, but which, as long as it continues to circulate 
with the ordinary stream of lymph, cannot be regarded 
as really perfect fibrine. This is a substance, of which I 
had demonstrated the presence in various exudations, 
especially in pleuritic fluids, long before my attention had 
been drawn to its occurrence in lymph. 

In many forms of pleurisy the exudation long remains 
fluid, and a number of years ago a peculiar case came 
under my notice, in which on puncturiug the thorax a 
liquid was evacuated which was perfectly clear and fluid, 
but in a short time after its evacuation had its whole 





FIBRINE OF LYMPH. 193 


mass pervaded by a coagulum, as is often enough the 
case with fluids from the abdominal cavity. After I had 
removed this coagulum from the liquid by stirring it, in 
order to convince myself of its identity with ordinary 
fibrine, the next day a fresh coagulum displayed itself, 
and this took place also on the following days. This co- 
agulative power lasted fourteen days, although the ope- 
ration had been performed in the midst of the heat of 
summer. This therefore was a phenomenon essentially 
_ differing from the ordinary coagulation of the blood, and 
somewhat difficult to explain upon the supposition that 
real fibrine existed completely developed in the fluid, 
but it seemed to indicate that it was only under the influ- 
ence of the atmospheric air that the fibrine was produced 
from a substance which must indeed have been nearly 
related to fibrine, but yet could not be real fibrine. I 
therefore propose to give it the distinctive name of fibri- 
nogenous substance, and when I afterwards had come to 
the conclusion that it was the same substance which we 
find in lymph, I was enabled to extend my view so as to 
include the proposition, that in lymph also fibrine is not 
contained in a perfect form. 

This same substance, which is distinguished from ordi- 
nary fibrine by its requiring to be a longer or shorter 
time in contact with atmospheric air before it can become 
coagulable, is also found under certain circumstances in 
the blood of the peripheral veins, so that even by an 
ordinary venzesection performed on the arm blood may 
be obtained, distinguished from ordinary blood by the 
slowness of its coagulation. Polli named this coagula- 
tive substance brady-fibrine. Such cases occur especially 
in inflammatory diseases of the respiratory organs, and 
most frequently give rise to the formation of a buffy coat 
(crusta pleuritica, crusta phlogistica). You all know that 


the ordinary crusta phlogistica forms in the blood of 
13 


194 LECTURE VIII. 


pneumonia or pleurisy the more readily the greater the 
wateriness of the liquor sanguinis, and the poorer the blood 
is in solid constituents, but it is an essential requisite that 
the fibrine should coagulate slowly. If the duration of 
the process be noted watch in hand, the conviction will 
soon be acquired that a very much longer time passes 
than is requisite for ordinary coagulation. From this 
frequent phenomenon, as it is met-with in the ordinary 
formation of a crust upon the surface of inflamed blood, 
gradual transitions are observed to a greatly increased 
prolongation of the period during which fluidity is re- 
tained. 

The most extreme instance of this kind as yet known 
occurred in a case observed by Polli. In a vigorous man, 
suffering from pneumonia, who came under treatment in 
the summer, at a time which does not offer the external 
conditions most favourable to slowness of coagulation, the 
blood, which flowed from the opened vein, took a week 
before it began to coagulate, and not until the end of a 
fortnight was the coagulation complete. In this case, 
too, occurred the other phenomenon which I had ob- 
served in the pleuritic exudations, namely, that decom- 
position (putrefaction) took place in the blood at an 
unusally late period in proportion to this lateness of 
coagulation. 

Now since phenomena of this kind are observed to 
occur with especial frequency in chest affections, a fre- 
quency so especial indeed that the buffy coat was long 
since designated Crusta pleuritica, there would seem. to 
be some grounds for inferring from this, that the function 
of respiration has a definite influence upon the occur- 
rence or non-occurrence of the fibrinogenous substance 
in the blood. At all events, the peculiarity possessed by 
the lymph is under certain circumstances transmitted to 
the blood, so that either the whole of the blood partakes 





FIBRINE REGARDED AS A LOCAL PRODUCTION. 195 


of it, and that in a higher degree, the greater the disturb- 
ance under which the respiration labours; or, in addi- 
tion to the ordinary, quickly coagulating matter, a second 
which coagulates more slowly is found. It frequently 
happens, namely, that two sorts of coagulation subsist 
side by side in the same blood, one early and the other 
late, especially in the cases in which direct analysis shows 
an increase of fibrine, a hyperinosis. These hyperinotic 
conditions appear therefore to indicate that in them an 
increased supply of lymphatic fluid is introduced into the. 
blood, and that the matters which are afterwards found 
in the blood are not the products of an internal transfor- 
mation of its constituents, and that therefore the ori- 
ginal source of the fibrine must not be sought for in the 
blood itself, but in those parts from which the lymphatic 
vessels convey the increased supply of fibrine. 

In explanation of these phenomena, I have ventured to 
advance the hypothesis, somewhat bold perhaps, though 
I consider it perfectly able to sustain discussion, namely, 
that fibrine generally, wherever tt occurs in the body exter- 
nal to the blood, is not to be regarded as an excretion from 
the blood, but as a local production ; and I have endea- 
vored to introduce an important change in the views en- 
tertained with regard to the so-called phlogistic crasis in 
relation to its localization. Whilst it had previously been 
the custom to regard the altered composition of the blood 
in inflammation as a condition existing from the very 
outset, and especially denoted by a primary increase in 
the fibrine, I on the contrary have shown the crasis to 
be an occurrence dependent upon the local inflammation. 
Certain organs and tissues have inherent in them in a 
higher degree the power of producing fibrine and of fa- 
vouring the occurrence of large quantities of fibrine in 
the blood, whilst other organs are by far less adapted 
for its production. 


196 LECTURE VIII. 


I have, moreover, pointed out the fact, that those or- 
gans which with especial frequency exhibit this peculiar 
combination of a so-called phlogistic state of the blood 
with a local inflammation are generally abundantly pro- 
vided with lymphatic vessels and connected with large 
masses of lymphatic glands, whilst all those organs which 
either contain very few lymphatics, or in which these 
vessels are scarcely known to exist, do not exercise any 
influence worth naming upon the amount of fibrine in 
the blood. Former observers had already remarked 
that there were inflammations occurring in very import- 
ant organs, as for example, in the brain, in which the 
phlogistic crasis was, properly speaking, not at all met 
with. Now it is precisely in the brain that we have 
scarcely any evidence of the existence of lymphatics. In 
those cases, on the contrary, in which the composition of 
the blood is earliest altered, namely, in diseases of the 
respiratory organs, we find an unusually abundant net- 
work of lymphatics. Not merely the lungs are pervaded 
by, and covered with, them, but the pleura also has ex- 
tremely numerous connections with the lymphatic sys- 
tem, and the bronchial glands constitute almost the great- 
est accumulations of lymphatic-gland substance possessed 
by an organ in the whole body. 

On the other hand, we are acquainted with no fact 
which shows it to be possible that, in consequence of a 
simple increase of the pressure of the blood, or of a 
simple change in the conditions which influence its cir- 
culation, an exudation of fibrinous fluids could in any 
organ take place into its parenchyma, or upon its sur- 
face, from the blood. It is certainly generally imagined 
that, when the current of the blood attains a certain 
strength, fibrine begins to appear in the exudation, but 
this has never been proved by experiment. Nobody has 
ever been able, by the production of a mere change in 


LOCAL FORMATION OF FIBRINE. 197 


the force of the current of the blood, to induce the 
fibrine to transude directly as it is wont to do in certain 
inflammatory processes; for this some irritation is 
always required. The greatest obstructions may be in- 
duced in the circulation, exudations of serous fluids may 
be experimentally produced upon the largest scale, but 
that peculiar fibrinous exudation which the irritation of 
certain tissues provokes with so much ease, never ensues 
upon these occasions. 

That the fibrine in the blood itself is produced by a 
transformation of the albumen, is a chemical theory, 
which has no other evidence in its favour than the fact 
that albumen and fibrine have a strong chemical resem- 
blance, and that, on comparing the questionable formula 
for fibrine with the equally questionable one for albu- 
men, it is very easy to imagine how, by the abstraction 
of a couple of atoms, the transition from albumen to 
fibrine might be effected. But our being able in this 
manner to deduce one of the formule from the other 
does not afford the slightest proof that an analogous 
transformation occurs in the blood. It may possibly 
take place in the body, but even then it would at any 
rate be more probable that it was accomplished in the 
tissues, and that from them the fibrine was conveyed 
away into the blood by means of the lymph. This "is, 
however, the more doubtful, because rational formule 
for the chemical composition of albumen and fibrine have 
not yet been determined, and the incredibly high atomic 
numbers in the empirical formule point to a very com- 
plex grouping of the atoms. 

Let us therefore hold fast the well-ascertained fact 
that fibrine can only be made to exude upon any surface 
by the occurrence of some irritation, that is, local 
change, in addition to the disturbance in the circulation. 
This local change, however, is, as results from experi- 


198 LECTURE VIII. 


ment, alone sufficient to cause the exudation of fibrine, 
- even when no obstruction arises in the circulation. Such 
obstruction is not therefore in any way needed in order 
that the production of fibrine may commence at any 
given point. On the contrary, we see that the cause of 
the greatest differences in the nature of exudations is to 
be found in the special constitution of the irritated parts. 
On the simple application of an irritating substance to 
the surface of the skin, there arises, when the irritation, 
whether chemical or mechanical in its nature, is only 
slight in degree, a vesicle, a serous exudation. If the 
irritation is more violent, a liquid exudes, which in the 
vesicle appears quite fluid, but coagulates after its eva- 
cuation. If the fluid from a blister raised by a cantha- 
rides-plaster be received into a watch-glass and exposed 
to the air, a coagulum forms, showing that there is 
fibrinogenous substance in the fluid. But we sometimes 
meet with conditions of the body, in which an external 
stimulus is sufficient for the production of blisters con- 
taining a fluid which directly coagulates. I had, last 
winter, a patient in my wards, whose feet had remained 
na state of ansesthesia ever since they had been frozen, 
and I employed as a remedy, amongst other things, 
local baths containing aqua regia. After a certain num- 
bér of these baths, blisters, which varied in diameter up 
to two inches, and were found, when opened, to be filled 
with large, jelly-like masses of coagulum, formed upon 
every occasion on the anesthetic part of the soles of the 
feet. In other persons probably ordinary blisters would 
have formed, containing a fluid, which would not have 
coagulated until after its evacuation. Such a difference 
manifestly depends upon a difference, not in the com- 
position of the blood, but in the disposition of the part 
affected. The difference between that form of pleurisy, 
which from its very commencement furnishes coagulable 


LOCAL FORMATION OF FIBRINE. : 199 


and coagulating fluids, and that in which the exudation 
is coagulable, but not coagulating, certainly points to - 
peculiarities in the local irritation. 

I do not think therefore that we are entitled to con- 
clude that in a person who has an excess of fibrine in his 
blood, there is on that account also a greater tendency to 
fibrinous transudation ; on the contrary, I should rather 
expect that in a patient who produces at a certain point 
a large quantity of fibrine-forming substance, much of 
it would pass from that point into the lymph and finally 
into the blood. The exudation may therefore in such 
cases be regarded as the surplus of the fibrine formed zn 
loco, for the removal of which the lymphatic circulation 
did not suffice. As long as the current of lymph does 
suffice, all the foreign matters which are formed in the 
irritated part are conveyed into the blood ; but, as soon 
as the local production becomes excessive, the products 
accumulate, and in addition to the hyperinosis, a local 
accumulation of fibrinous exudation will also take place. 
On account of the shortness of the time which is allotted 
to us, we cannot follow up this subject in its whole 
extent, but still I hope that you will at least completely 
grasp the fundamental idea which has guided me. Here, 
too, we have another example of that dependence of a 
dyscrasia upon a local disease to which I but a. short 
time ago called your attention as being the most impor- 
tant result of all our investigations concerning the blood. 

Now it is a very remarkable fact, and one which adds 
weight to this very view of mine, that it is very rarely 
that a considerable increase of fibrine takes place without 
a simultaneous increase in the colourless blood-corpuscles, 
and that therefore the two essential constituents which 
we find in the lymph we again meet with in the blood. 
In every case of hyperinosis we may rely upon discover- 
ing an increase in the colourless corpuscles, or, in other 


200 LECTURE VIII. 


words, every irritation of a part, which is abundantly 
provided with lymphatics, and freely connected with 
lymphatic glands, occasions also the introduction of large 
numbers of colourless cells (lymph-corpuscles) into the 
blood. 

This fact is especially interesting, inasmuch as you 
will perceive from it, that not only organs richly pro- 
vided with lymphatic vessels can occasion this increase, 
but that certain processes also are more calculated than 
others to lead to the introduction of considerable quantities 
of these elements into the blood, namely all those which 
are early conjoined with serious disease in the lymphatic 
system. If you compare an erysipelatous, or a diffuse 
phlegmonous (according to Rust pseudo-erysipelatous), 
inflammation in its effects upon the blood with a simple 
superficial inflammation of the skin, such as occurs in the 
course of the ordinary acute exanthemata, or after trau- 
matic or chemical irritation, you will at once see how 
great the difference is. Every erysipelatous or diffuse 
phlegmonous inflammation has the peculiarity of early 
affecting the lymphatic vessels and producing swellings 
in the lymphatic glands. In such a case we may feel 
assured that an increase in the number of the colourless 
corpuscles is taking place. Further, we find the signifi- 
cant fact, that there are certain processes which simul- 
taneously cause an increase of fibrine and colourless cor- 
puscles, and others again which only occasion an increased 
production of the latter. To this latter category belong 
the whole series of simple diffuse inflammations of the 
skin, in which also no considerable formation of fibrine 
takes place in the diseased parts. On the other hand, a 
number of conditions belong to it, which with regard to 
the quantity of fibrine may be designated as hypinoti- 
cal, all the processes namely which belong to the typhoid 
class, and agree in producing considerable swelling now 


LEUCOCYTOSIS AND LEUKAM.A. 201 


of one, and now of another, kind in the lymphatic glands, 
but do not produce any local exudation of fibrine. Thus 
typhoid fever causes these changes not only in the spleen, 
but also in the mesenteric glands. 

The condition in which the increased proportion of 
colourless corpuscles in the blood appears to be depend- 
ent upon an affection of the lymphatic glands, I have de- 
signated by the name of Leucocytosis. Now you know 
that another matter has long been the subject of my stu- 
dies, the affection named by me Leukemia, and our next 
business must be to determine how far genuine leuke- 
mia differs from these leucocytotical conditions. In the 
very first cases of leukeemia which came before me, a very 
essential property was discovered to exist, namely, that 
there was no essential variation in the proportion of 
fibrine in the blood. Afterwards it was found out that 
the proportion of fibrine might, according to the parti- 
cular circumstances of the case, be greater or less than, 
or the same as, usual, but that a continually augmenting 
increase of the colourless blood-corpuscles invariably took 
place ; and that the coincidence of this increase with a 
diminution in the number of the coloured (red) corpus- 
cles became more and more marked, so that as a final 
result a condition was attained, in which the number of 
the colourless corpuscles was almost equal to that of the 
red ones, and striking phenomena were displayed, even 
when the coarser modes of observation were employed. 
Whilst in ordinary blood we can seldom count more than 
one colourless corpuscle to about three hundred coloured 
ones, there are cases of leukeemia in which the increase 
of the colourless ones reaches such a height, that to every 
three red corpuscles there is one colourless one, or even 
two; or in which indeed the greater numbers are in 
favour of the colourless corpuscles. 

In dead bodies the increase in the colourless corpus- 


902 LECTURE VIII. 


cles generally appears more considerable than it really is, 
from reasons which I but a short time ago pointed out 
to you (p. 184); for these corpuscles possess extraordi- 
nary adhesiveness and accumulate in considerable masses 
wherever there is a retardation in the stream of blood, 
so that in the dead body the greatest number is always 
found in the right heart. Once, before I left Berlin, this 
singular case occurred to me, that, when I punctured 
the right auricle, the physician who had treated the case 
cried out, astonished, ‘‘ Why, there’s an abscess there !” 
So like pus did the blood appear. This puriform condi- 
tion of the blood does not indeed pervade the entire cir- 
culating stream ; the whole of the blood never looks like 
pus, because a comparatively large number of red cor- 
puscles always continues to exist; stillit sometimes hap- 
pens that blood flowing from a vein even during life 
éxhibits whitish streaks, and that, when the fibrine has 
been removed by stirring, and the defibrinated blood is 
allowed to stand,a voluntary separation at once takes 
place, the whole of the blood-corpuscles, red and colour- 
less, gradually sinking to the bottom of the vessel, and there 
forming a double sediment, a lower red stratum, covered 
by an upper, white and puriform one. This is explained 
by the difference in the specific gravity of the two kinds 
of corpuscles and the time they take to sink (p. 186). In 
this way too we are enabled very readily to distinguish 
leukemic from chylous (lipeemic) blood in which a milky 
appearance of the liquor sanguinis is produced by the 
admixture of fat, for, if the fibrine be removed, after 
some time there forms not a white sediment, but a 
cream-like layer on the surface. 

In the histories of all the known cases of leukemia we 
only find it once as yet recorded that the patient, after 
he had been for some time the subject of medical treat- 
ment, left the hospital considerably improved in health. 


| 


LEUKAMIA. 203 


In all the other cases the result was death. I do not 
wish by any means to infer from this that the disease in 
question is absolutely incurable ; I hope on the contrary 
that for it too remedies will at length be discovered ; but 
it is certainly a very important fact that we have in it, 
much, as in the progressive atrophy of muscles, to deal 
with conditions, which, when abandoned to themselves, 
or subjected to any one of the hitherto known methods 
of treatment, continually grow worse and ultimately lead 
to death. These cases possess, in addition, the remark- 
able peculiarity that, usually towards the close of life, a 
genuine hemorrhagic diathesis is developed and hemor- 
rhages ensue, which occur with especial frequency in the 
nasal cavity (under the form of exhausting epistaxis) but 
may also, under certain circumstances, take place in 
other parts of the body, as for example on a very large 
scale in the form of apoplectic clots in the brain, or of 
melena in the intestinal canal. 

Now, upon investigating whence this curious change in 
the blood takes its origin, we find in the great majority 
of cases that it is a certain, definite organ which presents 
itself over and over again with convincing constancy as 
the one essentially diseased, an organ which frequently, 
even at the outset of the malady, forms the chief object 
of the complaints and distress of the patients, namely, 
the spleen. In addition, a number of lymphatic glands 
are very frequently diseased, but the affection of the 
spleen stands in the foreground. Only in a few cases 
have I found the change in the spleen the less and that 
in the lymphatic glands the more prominent, and in 
these, matters had proceeded to such a pitch, ' that 
lymphatic glands, at other times scarcely observable, had 
developed themselves into lumps the size of walnuts, and 
that indeed in some few places there appeared to be 
scarcely anything else than glandular substance. Of the 


904 LECTURE VIII. 


glands which lie between the inguinal and lumbar glands 
we are wont to hear but little, nor have they indeed even 
a suitable name. Some of them lie in the course of the 
iliac vessels, and some in the real pelvis. But in two of 
these cases of leukeemia I found them so enlarged that 
the whole cavity of the pelvis proper was, as at were, 
stuffed full of glandular substance, between which the 
rectum and the bladder only just dipped in. 

I have therefore distingushed two forms of leukemia, 
namely, the ordinary splenic, and the lymphatic, form, 
which are certainly not unfrequently combined. The 
distinction rests not only upon the circumstance, that in 
the one case the spleen, in the other the lymphatic glands, 
constitute the starting point of the disease, but also upon 
the fact that the characteristic morphological elements 
which are found in the blood are not precisely similar. 
Whilst namely in the splenic forms these elements are 
generally comparatively large and perfectly developed 
cells with one or more nuclei, and in many cases bear a 
particularly great resemblance to the cells of the spleen, 
we notice in the well-marked lymphatic forms that the 
cells are small, the nuclei large in proportion and single, 
usually sharply defined, with dark outlines and somewhat 
granular, whilst the cell-wall is frequently in such close 
apposition to them that an interval can scarcely be de- 
monstrated. In many instances it looks as if perfectly 
free nuclei were contained in the blood. In these (the 
lymphatic) cases, therefore, it seems that the enlarge- 
ment of the glands alone, which is accompanied in its 
progress by a real increase in the number of their ele- 
ments (hyperplasia), also conveys a larger number of cel- 
lular elements into the lymph and through this into the 
blood, and that, just in proportion to the predominance 
of these elements, the formation of the red cells suffers 
obstruction. This is in a few words the history of these 


HYPERINOSIS, LEUCOCYTOSIS AND LEUKAMIA. 905 


processes. Leuksemia is thus a sort of permanent, pro- 
gressive leucocytosis, whilst this on the other hand in its 
simple forms constitutes a transitory process, connected 
with fluctuating conditions in certain organs. 

You see therefore that there are at least three different 
conditions here, bordering one upon the other : hyperino- | 
sis, leucocytosis and leuksemia, between which and the 
lymphatic fluids there exists an intimate connection. 
The one series, that namely which is distinguished by an 
increase in the quantity of fibrine, is rather to be referred 
to the accidental condition of the organs from which the 
lymphatic fluids are derived, whilst those states which are 
induced by an increase in the number of cellular ele- 
ments are rather regulated by the condition of the glands 
through which these fluids have flowed. These facts can 
hardly, I think, be interpreted in any other manner than 
by supposing that the spleen and lymphatic glands are 
really intimately concerned in the development of the 
blood. This has become still more probable since we 
have succeeded in obtaining chemical evidence also in 
support of it. Herr Scherer upon two occasions ex- 
amined leuksemic blood which I had submitted to him, 
in order to compare it with the matters he had discovered 
in the spleen, and the result was that hypoxanthine, 
leucine, uric, lactic, and formic, acid, were found there. 
In one case of leukemia a liver which I had kept for 
several days became entirely covered with granules of 
tyrosine ; in another, leucine and tyrosine crystallized in 
large masses out of the contents of the intestines. In 
short, everything points to an increased action in the 
spleen, which normally contains these substances in con- 
siderable quantity. 

A good many years elapsed (after 1845) during which 
I found myself pretty nearly alone in my views. .It has 
only been by degrees and indeed, as I am sorry to be 


206 LECTURE VIII. 


obliged to confess, in consequence rather of physiological 
than pathological considerations, that people have come 
round to these ideas of mine, and only gradually have 
their minds proved accessible to the notion, that in the 
ordinary course of things the lymphatic glands and the 
spleen are really immediately concerned in the produc- — 
tion of the formed elements of the blood ; and that in 
particular the corpuscular constituents of this fluid are 
really descendants of the cellular bodies of the lymphatic 
glands and the spleen which have been set.free in their 
interior and conveyed into the current of the blood. 
And let this serve as an introduction to the consideration 
of the question of the origin of the blood-corpuscles 
themselves. 

You will probably recollect, gentlemen, from the time 
of your studies, that the lymphatic glands used to be 
regarded as coils of lymphatic vessels. The afferent 
lymphatics may, as is well known, even with the naked 
eye be seen breaking up into smaller branches, disappear- 
ing within the glands, and finally again emerging from 
them. From the results of the mercurial injections 
which even in the last century were made with such 
great care, the only inference to be drawn appeared to 
be, that the afferent lymphatic vessel formed a number 
of convolutions, which interlaced in various ways and 
were finally continued into the efferent vessel, so that the 
gland was composed of nothing else than the thickly 
crowded coils of the afferent vessels. The whole atten- 
tion of modern histologists has been directed to the task 
of confirming this tortuous transit of the lymphatic ves- 
sels through the gland, but after many years of labour 
spent in vain, the attempt was at length abandoned. 

At the present moment there is, I should suppose, 
scarcely an histologist who believes in the perfect conti- 
nuity of the lymphatic vessels throughout the gland, but 











STRUCTURE OF LYMPHATIC GLANDS. 207 


Kélliker’s view is generally adopted, that the lymphatic 
glands interrupt the current of the lymph, the afferent 
vessel resolving itself into the parenchyma of the gland 
~ and reconstituting itself out of it. This condition we 
cannot well compare with anything else than a kind of 
filtering apparatus, something like our ordinary sand or 
charcoal filters. 

When a gland is cut across, a structure is frequently 
brought to view resembling that of a kidney. At those 
points where the afferent vessels break up, a firmer sub- 
stance is seen to lie, half surrounded by which a kind of 
hilus marks the spot at which the lymphatic vessels again 
forsake the gland. Here there is found a reticular tissue 
with an often distinctly areolar or cavernous structure, 
into which, besides the efferent lymphatic vessels, blood- 
vessels also enter on their way into the proper substance 
of the gland. Kolliker has accordingly distinguished a 
cortical and a medullary substance ; but the so-called 
medullary substance scarcely retains the character of 
glandular tissue. This is found chiefly in the cortical 
substance, which is of greater or less thickness, and it is 
therefore best to call the medullary substance simply the 
hilus, since afferent and efferent vessels lie there in close — 
contact, just as in the hilus of the kidneys the ureters and 
veins emerge, whilst the arteries enter. The essential 
part of the gland is therefore the periphery, the often 
kidney-like cortical substance. 

_In this can be distinguished, whenever the gland is at 
all well developed (and in some cases of pathological en- 
largement it is extremely distinct) even with the naked 
eye, little, roundish, white or grey granules lying side 
by side. When the part is moderately well filled with 
blood, around each granule may be pretty nearly 
always discerned a red circle of vessels. These granules 
have long been called follicles, but it was doubtful 


208 LECTURE VIII. 


whether they were distinct formations or mere convolu- 
tions of the lymphatic vessel protruding on the surface. 
Upon more delicate microscopical 
examination, the proper (glandu- 
lar) substance of the follicles can 
easily be distinguished from the 
fibrous meshwork (stroma) which 
bounds them on all sides, and is 
externally continuous with the 
connective tissue of the capsule. 
The internal substance is chiefly 
composed of little cellular ele- 
ments, which lie pretty loosely, 
being merely enclosed in a fine 
network of star-shaped, often nu- 
cleated trabecule. If we attempt to search for the 
lymphatic vessels in the cortical substance, but very 
little can be discovered of them in the stroma, and if a 
gland be injected, the injection penetrates right into 
the middle of the follicles. If a mesenteric gland be 
examined during chylification, that is perhaps three or 
four hours after a meal at which fat has been taken in 
abundance, its whole substance appears white and per- 
fectly milky, and on examining individual parts of it 
microscopically, the minute fat-drops of the chyle may 
be detected every where lying between the cellular ele- 
ments of the follicles. It seems, therefore, that the cur- 
rent of lymph forces its way between these elements, and 








Fig. 61. Sections through the cortical substance of human mesenteric glands. 
A. View of the whole cortical substance slightly magnified: P, investing adipose 
tissue and capsule, through which blood-vessels v, v, v enter. F, F, F. Follicles of 
the gland, into which the blood-vessels in part plunge, at i, 7 the interstitial tissue 
separating the follicles (stroma). 

B. More highly magnified (280 times). C. The tissue of the capsule with paral- 
lel fibrils. a, a. The reticulum, partly empty, partly filled with the nucleated con- 
tents. The whole corresponds to the outer part of a follicle. 





STRUCTURE OF LYMPHATIC GLANDS. 209 


that no really free channel for it exists, seeing that the 
elements lie crowded together like the particles in a 
charcoal filter, so that the lymph trickles out again on 
the other side in a more or less purified state. The fol- 
licles should accordingly be regarded as spaces filled with 
cellular elements but variously intersected by a trabecu- 
lar network, and thus they can no longer be held to be 
convolutions or dilatations of the lymphatics, but must 
be viewed as interposing themselves in the course of 
these vessels after they have broken up into a series of 
ramifications continually increasing in minuteness. 

Of the minute elements contained in the follicles, the 
cells of the parenchyma, some appear to become separated 





08 


and afterwards to mingle with the blood as colourless 
blood- or lymph-corpuscles. The more the glands be- 
come enlarged, the more numerous are the cellular ele- 
ments which pass into the blood, and the larger and more 
perfectly developed are the individual colourless cells of 
the blood wont to be. 

The same condition seems to prevail in the spleen. 
Originally we all imagined that the veins were the chan- 


Fig. 62. Lymph-corpuscles from the interior of the follicles of a lymphatic gland. 
A. As usually seen; a, free nuclei, with and without nucleoli, simple and divided. 
b. Cells with smaller and larger nuclei, which are .closely invested by the cell-wall. 
B. Enlarged cells from a hyperplastic bronchial gland in a case of variolous pneu- 
monia (comp. in Fig. 57 the colourless blood-corpuscles from the same source). 4. 
Largish cells with granules, and single nuclei. 6. Club-shaped cells. ¢. Larger 
cells with larger nuclei and nucleoli. d. Division of nuclei. e. Club-shaped cells 
in close apposition (cell-division?). ©. Cells with an endogenous brood. 300 
diameters. 


14 


210 LECTURE VIII. 


nels by which the colourless corpuscles were conveyed 
away from the spleen; but in this instance also I have 
eome to the conclusion that their removal is in all proba- 
bility effected by means of the lymphatic vessels. 


(LET enn tx, 


wages MARCH 13, 1858. 


PYAIMIA AND LEUCOCYTOSIS. 


Comparison between colourless blood- and pus-corpuscles—Physiological re-absorp- 
tion of pus; incomplete (inspissation, cheesy transformation), and complete 
(fatty metamorphosis, or milky transformation). Intravasation of pus. 

2us in the lymphatic vessels—Retention of matters in the lymphatic glands—Me- 
chanical separation (filtration)—Coloration by tattooing—Chemical separation 
(attraction): Cancer, Syphilis—Irritation of lymphatic glands, and its relation to 
leucocytosis. 

Digestive and puerperal (physiological) leucocytosis—Pathological leucocytosis 
(Scrofulosis, typhoid fever, cancer, erysipelas). 

Lymphoid apparatuses: solitary and Peyerian follicles in the intestines—Tonsils 


and follicles of the tongue—Thymus—Spleen. 
Yomplete rejection of pyemia as a dyscrasia susceptible of demonstration morpho- 


logically. 


4 


f/f 

‘In a practical point of view the question of pyamia) 
forcibly intrudes itself upon us in connection with the 
changes which we have last considered, and as this must 
still be reckoned among the most controvertible of sub- 
jects, you will, I hope, allow me to ae 8 a little more 
particularly into its details. 

What is to be understood by pyemia? It has gene- 
rally been conceived to be a condition, in which tke 
blood contains pus, and as pus is essentially characterized 
by its morphological constituents, what is meant of 
course is, that pus-corpuscles are to be seen in the blood. ; 


( Now that we have found out, however, that the colour- 
211 


212 LECTURE IX. 


less corpuscles of the blood as they usually appear and 
are to be observed in people in the best state of health, 
resemble pus-corpuscles in every respect (p. 180), one 
essential point in the question is thus at the very se 
got rid of. In order, however, to render the subject to | 
some extent perspicuous, it is necessary to enter into the 
consideration of the different points of view which are 
here involved a little more in detail. } 

Colourless blood-cells are so like pus-corpuscles as easily 
to be mistaken for them, so that if im any specimen we 
meet with such elements, we can never say with certainty 
off-hand whether we have to deal with colourless blood-, 
or pus-corpuscles. Formerly, and to some extent even 
up to our own times, the view was very generally enter- 
tained that the constituents of pus pre-existed in the 
blood ; that pus was only a kind of secretion from the 
blood, in somewhat the same way that urine is ; and that 
it could also like a simple fluid return into the blood. 
This view explains, you see, the conception which has 
been so long preserved in the doctrine of the so called 
physiological reabsorption of pus. 

It was imagined that the pus might be again taken up 
into the blood from the different points at which it had 
been deposited, and that a favourable turn was thereby 
effected in the disease, inasmuch as the reabsorbed pus 
was thus at last removed from the body. The tale went 
that in the case of a patient with pus in the cavity of the 
pleura the disease might terminate in the evacuation of 
purulent urine or purulent feeces, without the pus having 
previously made its way directly from the pleura into the 
urinary passages or the intestinal canal. It is therefore 
admitted to be possible that pus may be reabsorbed and 
conveyed away in substance. Afterwards, when the doc- 
trine of pyemia had more and more gained ground, these 
cases were distinguished by the name of physiological re- 


REABSORPTION OF PUS. —- 98 


absorption of pus, from that which was considered to be 
pathological, and the only question that remained was, 
in what way the first process with its favourable and the 
second with its malignant issue could be accounted for. 
This matter finds its simple solution in the fact that pus 
as pus is never reabsorbed. There is no form, by which 
pus in substance can disappear by the way of reabsorp- 
tion ; it is always the fluid part of the pus which is taken 
up, and therefore what is called the reabsorption of pus 
may be referred to the two following possibilities. : 

In the first case, the pus with its corpuscles is at the 
time of the reabsorption still more or less intact. Then 
the pus becomes of course thicker in proportion as the 
fluid disappears. This constitutes the long known thick- 
ening (inspissation) of pus, whereby is produced what the 
French term ‘‘ pus concret,” which consists of a thick 
mass, containing the pus-corpuscles in a shrivelled con- 
dition, when not only the fluid between the pus-corpus- 
cles (pus-serum) but a part also of that present in them 
has disappeared. 





_ Fig. 63. A. Pus-corpuscles, a fresh, 6 after the addition of a little water, c—e 
after treatment with acetic acid, the contents cleared up, the nuclei which were in 
process of division, or already divided, visible, at e with a slight depression on 
their surface. B. Nuclei of pus-corpuscles in gonorrhea; a simple nucleus with 
nucleoli, 4 incipient division, with depressions* on the surface of the nuclei, ¢ pro- 
gressive bi-partition, d tri-partition. C. Pus-corpuscles in their natural position 
with regard to one another. 500 diameters. 


* By many held to be nucleoli, 


214 LECTURE IX. 


Pus consists essentially of cells, which in their ordinary 
condition lie close to one another (Fig. 63, C, and be- 
tween which a small quantity of intercellular fluid (pus- 
serum) exists. Within the pus-corpuscles themselves lies 
a substance which is likewise provided with a great quan- 
tity of water ; for nearly every specimen of pus, although 
it may look very thick when fresh, contains such a large 
amount of water that it loses a great deal more by eva- 
poration than a corresponding quantity of blood. The 
latter only gives the impression of being more watery 
because it contains a great deal of free (intercellular), 
- but relatively little intracellular, fluid, whilst in pus on the 
contrary there is a greater quantity of water in the cells, 
and less without them. When then reabsorption takes 
place, the greatest part of the intercellular fluid first dis- 
appears, and the pus-corpuscles draw nearer to one an- 
other ; soon, however, a part of the fluid from the cells 

themselves also vanishes, and in propor- 

tion as this is the case, they become 
b smaller, more irregular, angular, and un- 
‘&~ even, they assume the most singular 
forms, lie closely pressed together, re- 
fract the light more strongly on account 
of their containing a greater quantity of 
solid matter, and present a more homogeneous appear- 
ance. 

This kind of inspissation is by no means so rare a pro- 
cess as it is often assumed to be, but on the contrary of 
‘extremely frequent occurrence, and almost even more 
important than frequent. This is namely one of the pro- 
cesses which lead to the formation of the much discussed 





Fig. 64. Inspissated, cheesy pus. a. Shrivelled pus-corpuscles, diminished in 
size, somewhat distorted, and looking more homogeneous and solid than usual. 
6. Similar corpuscles with fat granules. c¢. Their natural position with regard to 
one another. 300 diameters. 





INSPISSAT ION (TUBERCULIZATION) OF PUS. 915 


cheesy products which have recently been all included 
under the term tubercle, and concerning which it has 
been shown, especially by Reinhardt, that they must to 
a very considerable extent really be referred to pus as 
their origin, and therefore be regarded as inflammatory 
products. Hereafter, we shall see that these observa- 
tions have been employed for the deduction of false con- 
clusions concerning tubercle itself; but that by inspissa- 
tion inflammatory products can be converted into things 
which are called tubercles, is indubitable. It is precisely 
in the history of pulmonary tuberculosis that this opera- 
tion plays a very prominent part. You have only to 
imagine shrivelled-up cells like these inclosed within the 
alveoli of the lungs and undergoing inspissation of their 
contents in one alveolus after another, and you will at 
length obtain a cheesy hepatization such as is usually 
described under the name of tubercular infiltration.. 

This imperfect reabsorption, in which only the fluid 
constituents are reabsorbed, leaves the mass of solid con- 
stituents lying in the part as a caput mortuum, as a mass 
deprived of vitality and no longer capable of life. This 
is the kind of inspissation which we see occur on a large 
scale in the case of*imperfect reabsorption of pleuritic 
exudations, when very large layers of a crumbling sub- 
stance remain behind in the sac of the pleura; and also 
round about the vertebral column in caries of the verte- 





Fig. 65. Inspissated hemorrhagic pus from a case of empyema, some of it in pro- 
cess of disintegration. a. The natural mass, containing granular débris, shrivelled 
pus- and blood-corpuscles. 6. The same mass treated with water; a few granular, 
decolorized blood-corpuscles have become evident, c¢ and d. After the addition of 


acetic acid, 800 diameters, and at d 520, 
+ 


216 LECTURE IX. 


bree (Spondylarthocace), cold abscesses, ete. In all 
these cases the reabsorption is at an end as soon as the 
fluid has disappeared. Herein consists the evil import 
of these processes. For the solid parts which are not 
reabsorbed, either remain lying in the part as such, or 
they may afterwards soften, in which case, however, they 
do not usually undergo reabsorption, but for the most 
part give rise to ulceration. At all events what is reab- 
sorbed is not pus, but a simple fluid composed in great 
part of water, a few salts, and a very small quantity of 
albuminous matter, and there can be no question but 
that we have here presented to us one of the most incom- 
plete forms of reabsorption. 

The second form of purulent Fenbecrp Gon | is that which 
constitutes the most favourable case, when the pus really 
disappears and no essential part of it need remain be- 
hind. But here too the pus is not reabsorbed as pus, 
but first undergoes a fatty metamorphosis ; every single 
cell sets fatty particles free within it, 
breaks up and at last nothing further 
remains than fatty granules and inter- 
vening fluid. Then therefore there exist 
no longer either cells or pus ; and their 
place is occupied by an emulsive mass, a 
kind of milk, composed of water, some albuminous mat- 
ter and fat, and in which even sugar has on various occa- 
sions been demonstrated, whereby a still greater analogy 
with real milk is brought about. It is this pathological 
milk which afterwards comes to be reabsorbed—once 
more therefore not pus, but fat, water, and salts. These 
are the processes which may be denominated ‘ physiolo- 





Fig. 66. Pus engaged in retrograde fatty metamorphosis (fatty degeneration), a. 
Commencement of the change. 0. Fat-granule cells with nuclei still distinct. 
ce. Granule-globule (inflammatory globule). d. Disintegration of the globule. e. 
Emulsion, milky débris. 350 diameters. 

# 


PUS IN THE LYMPHATIC VESSELS. 217 


gical reabsorption of pus ;’ a reabsorption, in which pus 
is not reabsorbed as such, but either only its fluid consti- 
tuents, or its solid ones after they have been considerably 
altered by an internal transformation. 

There is however certainly one case in which pus in 
substance may become the object, not exactly of a reab- 
sorption, but at any rate of an itravasation, and where 
this intravasated pus may circulate within the vessels ; I 
mean the case in which a vessel receives a wound or is 
perforated and pus passes through the opening into its 
interior. An abscess may lie close to a vein, burst 
through the walls, and evacuate its contents into the ves- 
sel. Still more easily can such a transit be effected in 
lymphatic vessels which run into open abscesses. The 
only question therefore is how far we are entitled to con- 
sider this case as a frequent one. As far as the veins are 
concerned, the possibility of such an occurrence has been 
for the last twenty years confined within somewhat nar- 
row limits, and the notion of the reabsorption of pus in 
substance through the medium of the veins has been 
more and more abandoned ; but about its taking place 
by means of the lymphatics people still pretty fre- 
quently talk, and indeed they have frequently occasion 
to do so. 

But it is almost a matter of indifference whether the 
pus really finds its way into lymphatic vessels from the 
outside, or, whether, as others assume to be the case, it 
owes its origin to inflammation in the lymphatic vessels ; 
ultimately, the question is always this, how far a lymph- 
atic vessel filled with pus is capable of effecting an eva- 
cuation of its contents into the circulating stream of 
blood, and producing a genuine pyemia. The possibility 
of such an occurrence must as a rule be denied, and in- 
deed for a very simple reason. All the lymphatic ves- 
sels which are in a condition to take up pus in this way 


918 LECTURE IX. 


are peripheral ones, whether they arise from external or 
internal parts, and only after a somewhat lengthened 
course do they gradually reach the blood-vessels. In all, 
interruptions are formed by the lymphatic glands, and 
since we know that the lymphatic vessels do not pass 
through the glands as wide, tortuous, and interlacing 
canals (p. 208), but that, after they have broken up into 
fine branches, they enter into spaces which are filled with 
cellular elements, it is manifest, that no pus-corpuscle 
can pass a gland. 

This is a very important point of view which curiously 
enough is generally overlooked, although it meets with 
the best possible confirmation in the daily experience of 
the practical physician. In proof of the inevitable ob- 
struction to the passage of solid particles through the 
lymphatic glands, a very pretty experiment is afforded 
by a custom prevalent amongst the lower classes of our 
population, the well-known practice of tattooing the arms 
and occasionally other parts. When a workman or a 
soldier has a number of punctures made upon his arm, 
and arranged so as to represent letters, signs, or figures, 
nearly always, in consequence of the great number of 
punctures, some of the superficial lymphatic vessels are 
injured. It could not indeed well happen otherwise than 
that, when whole regions of skin are circumscribed by 
the pricks of a needle, at least some few lymphatic ves- 
sels should be hit upon. Afterwards a substance is rub- 
bed in which is insoluble in the fluids of the body, such 
as clinnabar, gunpowder, or the like, and which, remain- 
ing in the parts, causes a permanent coloration of them. 
But in the rubbing in a certain number of the particles 
find their way into lymphatic vessels, are carried along 
in spite of their heaviness by the current of lymph, and 
reach the nearest lymphatic glands, where they are sepa- 
rated by filtration. We never find that any particles are 





DEPOSITS IN LYMPHATIC GLANDS AFTER TATTOOING. 919 


conveyed beyond the lymphatic glands and make their 
way to more distant points, or that they deposit them- 
selves in any way in the parenchyma of internal organs. 
No, the mass always settles in the nearest group of 
glands. On examining the infiltrated glands it is easy to 
convince oneself that the size of the deposited particles 
is less than that even of the smallest pus-corpuscle. 


Fig. 67. 





In the object which I place before you (Fig. 67) the spot 

. has accidentally been hit upon, at which the lymphatic 
vessel enters into the gland, and whence, enclosed within 
the trabecule of connective tissue which are prolonged 
from the capsules between the follicles, it proceeds in a 
spiral form, and finally breaks up into its branches. Where 
these pass into the neighbouring follicles, which are here 


Fig. 67. Section through the cortical substance of an axillary gland from an arm, 
the skin of which had been tattooed. A large lymphatic vessel is seen entering 
from the cortical substance, gently winding and breaking up into fine branches. 
Round about are follicles, for the most part filled with connective tissue. The dark, 
finely granular mass represents the deposit of cinnabar, 80 diameters. 


220 LECTURE IX. 


indeed in great part filled with connective tissue, they 
have poured out the whole mass of cinnabar, so that in 
part it still lies within the intervening trabeculae, but yet 
in part has penetrated into the follicles themselves. The 
preparation comes from the arm of a soldier who had the 
figures rubbed in in 1809, so that the mass 
has remained nearly fifty years in the 
same place. None of it has penetrated 
farther than this spot; even the next 
layer of follicles does not contain any. 
The particles are however so small, and 
the majority of them so minute in com- 
parison with the cells of the gland, that 
they cannot at all be compared to pus- 
corpuscles. Now when such molecules as these are un- 
able to pass, when such extremely minute particles cause 
an obstruction, it would be somewhat bold to imagine 
that pus-corpuscles, which are relatively large, could 
effect a passage. 

This arrangement, gentlemen, by means of which the 
free current of fluid is interrupted in the lymphatic 
glands, and the coarser particles are retained there in 
quite a mechanical manner, admits, as may readily be 
conceived, of no other kind of reabsorption from the pe- 
riphery through the medium of the lymphatic vessels than 
that of simple fluids. We should indeed be mistaken, if — 
we were to consider the whole action of the lymphatic 
glands to consist merely in their being interposed like 
filters between the different portions of the lymphatic ves- 
sels. They have manifestly another part to play, inas- 
much as the substance of the glands indubitably takes up 


Fig. 68. 





Fig. 68. Reticulum of an axillary gland filled with cinnabar, from an arm which 
had been tattooed (Fig. 67). a. Part of an inter-follicular trabecula with a lymph- 
atic vessel; 6 one of its larger branches entering into a follicle; c, ¢ the anasto- 
mosing, nucleated networks of the reticulum; the dark granules are particles of 
cinnabar. 300 diameters, 





LYMPHATIC GLANDS IN CANCER AND SYPHILIS. 991 


into itself certain ingredients from the fluid mass of the 
lymph, retains them, and thereby also alters the chemi- 
cal constitution of the fluid, so that it quits the gland all 
the more altered because it must at the same time be 
assumed that the gland yields up certain constituents to 
the lymph, which did not previously exist in it. 

I will not here enter into minute details, since the his- 
tory of every malignant tumour affords the best examples 
in support of this position. When an axillary gland be- 
comes cancerous, after previous cancerous disease of the 
mamma, and when during a long period only the axil- 
lary gland remains diseased without the group of glands 
next in succession or any other organs becoming affected 
with cancer, we can account for this upon no other sup- 
position than that the gland collects the hurtful ingredi- 
ents absorbed from the breast, and thereby for a time 
affords protection to the body, but at length proves insuf- 
ficient, nay, perhaps at a later period itself becomes a 
new source of independent infection to the body, inas- 
much as a further propagation of the poisonous matter 
may take place from the diseased parts of the gland. 
Equally instructive examples are afforded by the his- 
tory of syphilis, in which a bubo may for a time become 
the depository of the poison, so that the rest of the eco- 
nomy is affected in a comparatively trifling degree. As 
-Ricord has shown, it is precisely in the interior of the 
real substance of the gland that the virulent matter is 
found, whilst the pus at the circumference of the bubo is 
free from it; only so far as the parts come into contact 
with the lymph conveyed from the diseased part, do they 
absorb the virulent matter. _ 

If we apply these facts to the reabsorption of pus, we 
are not, even in the case when it has really made its way 
into lymphatic vessels, at all entitled to conclude that as 
an immediate consequence of this irruption the blood be- 


229 LECTURE IX. 


comes infected with the constituents of pus ; on the con- 
trary a retention of the pus-corpuscles will probably take 
place within the glands, and even the fluids which suc- 
ceed in passing them, will during that passage lose a 
great part of their noxious properties. Secondary glan- | 
dular swellings show themselves in various forms after 
peripheral infection. How can they be explained other- 
wise than upon the supposition, that every contaminat- 
ing (miasmatic) substance, which is to be regarded as 
essentially foreign or, if I may so express myself, hostile, 
to the body, by penetrating into the substance of the 
gland, produces in it a state of more or less marked irri- 
tation which very frequently increases to a real inflam- 
mation of the gland? I shall hereafter revert to the sub- 
ject of irritation and enter a little more fully into the con- 
sideration of the meaning which should be attached to it, 
and I will therefore here only make this remark, that 
according to my investigations the irritation of a gland 
consists in its falling into a state in which there is an _ 
increased formation of cells in it—its follicles becoming 
enlarged, and after a time exhibiting a much greater 
number of cells than before. In proportion to the extent 
of these processes we then see the colourless elements of 
the blood also increase. Every considerable irritation of 
a gland is followed by an increase in the proportion of 
lymph-corpuscles in the blood, and every process there- 
fore which is accompanied by glandular irritation, will 
also have the effect of supplying the blood with larger 
quantities of colourless blood-corpuscles, or, in other 
words, of producing a leucocytotic condition. If then the 
opinion be entertained that pus has been absorbed, and 
that pus is the cause of the disturbances which have de- 
clared themselves, nothing is easier than to demonstrate 
the presence of cells in the blood which have the appear- 
ance of pus-corpuscles and are often present in such large 





LEUCOCYTOSIS CONFOUNDED WITH PY_EMIA. 223 


quantities as to form accumulations (Fig. 58) which may 
be seen, in the dead body, with the naked eye, looking 
like minute spots of pus; or as to constitute large, con- 
tinuous or granular layers on the inferior surface of the 
buffy coat of blood taken from a vein (Fig. 60). Appa- 
rently the proof is as plausible as possible. The observer 
_ starts with the supposition that pus has found its way into 
the blood ; he examines the blood and really discovers 
elements, having all the appearance of pus-corpuscles, and 
in very great numbers. Even if it be admitted that 
colourless blood-cells may look like pus-corpuscles, still 
the conclusion which has been repeatedly arrived at in 
cases of pyzemia, is very seductive, namely, that on ac- 
count of the great multitude, they cannot possibly be 
colourless blood-, but must be pus-corpuscles. This was 
the conclusion arrived at years ago by Bouchut on the 
occasion of an epidemic of puerperal fever which he then 
took to be pyzmia, but has very recently, founding his 
Opinion upon the same observations, declared to have 
been acute leukemia. It is moreover the same conclu- 
sion which Bennett came to in the much-discussed matter 
of priority between us, when he observed a case of in- 
dubitable leukemia some months before I saw my first 
case, and inferred from the presence of colourless corpus- 
cles in larger numbers than in any instance upon record, 
that it was a case of ‘‘suppuration of the blood.” This 
conclusion of his indeed was not original, but was based 
upon the hemitis of Piorry of which I lately spoke (p. 
187), this physician having conceived the blood itself to 
become inflamed and engender pus, a state which was 
afterwards denominated spontaneous pyzmia by the 
Vienna school. 

Now all these errors proceeded from the circumstance 
that such an enormously great number of colourless cor- 
_puscles were found in the blood. Now-a-days their 


224 LECTURE IX. 


occurrence can be just as simply explained according to 
our theory of hematopoiesis, as it previously seemed 
explicable only according to that of pyeemia. Irritation 
of the lymphatic glands explains without any difficulty 
the increase in the colourless, pus-like cells in the blood, 
and that too in all cases—not only in those where 
pyemia was expected to be found, but also in those 
where it was not expected, but where the blood, not- 
withstanding, exhibited the same quantity of colourless 
corpuscles as in genuine pyemia answering to our 
clinical notions of the disease. 

Thus it has been shown that every meal produces a 
certain state of irritation in the mesenteric glands, inas- 
much as the constituents of the chyle which are conveyed 
to these bodies, act as a physiological stimulus to them. 
The milk which we drink, the fatty matters in our soups, 
the various kinds of fat distributed in a state of minute 
division throughout the more solid articles of our food, 
find their way in the form of extremely minute globules 
into the lacteals and diffuse themselves there just like the 
cinnabar in the glands; but the smallest of the fatty 
molecules after a time force their way through the gland. 
For such minute bodies therefore there still exists a real 
permeability in the channels of the gland, but even they 
are for a time retained, and it always takes a long time 
before the mesenteric glands after a meal again become 
entirely free from fat, and the propulsion of this sub- 
stance through them is manifestly effected by a propor- 
tionately strong pressure. At the same time we observe 
an enlargement of the gland, and likewise after every 
meal an increase in the number of colourless corpuscles 
in the blood—a physiological leucocytosis, but no pyzemia. 

In proportion as pregnancy advances, as the lymphatic 
vessels in the uterus dilate, and the interchange of mate- 
rial in the organ increases with the development of the 





PHYSIOLOGICAL AND PATHOLOGICAL LEUCOCYTOSIS. 925 


foetus, the lymphatic glands in the inguinal and lumbar 
regions become considerably enlarged, and that some- 
times to such an extent, that, if we were to find them in 
a similar state at any other time, we should regard them 
as inflamed. This enlargement conveys into the blood 
an increased quantity of fresh particles of a cellular na- 
ture, and thus from month to month the number of 
colourless corpuscles augments. At the time of birth 
we may see in the defibrinated blood of nearly every 
puerperal woman, whether suffering from pyemia or not, 
the colourless corpuscles forming a pus-like sediment. 
This too is a physiological form which is far from being a 
pyzemic one. But if care be taken to select a puerperal 
woman, offering symptoms of disease which correspond 
with those usually presented by pyzemia, nothing is easier 
than to find these numerous colourless multi-nuclear cells, 
which are precisely, such as are supposed to corroborate 
the presence of pyzemia. These are fallacious conclu- 
sions which result from imperfect knowledge of the nor- 
mal conditions of life and development. As long as we 
are exclusively bent upon proving the presence of pyse- 
mia, all this may have the appearance of being a great and 
new occurrence, and we may, when we examine the 
blood of a woman in child-bed, consider ourselves justi- 
fied in concluding that she has pyzemia even before its 
symptoms declare themselves. But we may examine 
when we will, we shall always find some traces of leuco- 
cytosis, just as it has already long been known that it is 
very common for a buffy coat to form in the case of preg- 
nant women, because their blood generally has conveyed 
into it a larger quantity than usual of a more slowly con- 
tracting fibrine (hyperinosis). This is accounted for by 
the increased nutrition of the uterus, and by the changes, 
so nearly allied to inflammatory processes, which are go- 


ing on in the uterine system, and are associated with a 
15 


226 LECTURE IX. 


certain amount of irritation in the lymphatic glands im- 
mediately in connection with it. 

If we proceed a step farther and consider pathological 
cases, we meet with these leucocytotic conditions in the 
whole of that series of diseases which are complicated 
with glandular irritation, and in which the irritation does 
not lead to a destruction of the glandular substance. 
During the progress of an attack of scrofula, in which, 
if the disease run a somewhat unfavourable course, the 
glands are destroyed, either by ulceration, or cheesy 
thickening, calcification, etc., an increased introduction of 
corpuscles into the blood can only take place as long as 
the irritated gland is still in some degree capable of per- 
forming its functions, or still continues to exist ; as soon 
however as the gland is withered or destroyed, the for- 
mation of lymph-cells hkewise ceases and with it the leu- 
cocytosis. In all cases, on the other hand, in which a 
more acute form of disturbance prevails, connected with 
inflammatory tumefaction of the glands, an increase in 
the colourless corpuscles always takes place in the blood. 
So it is in typhoid fever, in which we observe such ex- 
tensive medullary (markige) swellings of the abdominal 
glands ; so it is in cancer patients, when irritation of the 
lymphatic glands manifests itself; so, lastly is it in the 
course of the processes which come under the denomina- 
tion of malignant erysipelas and are so early wont-to be 
accompanied by glandular swellings. Such is the mean- 
ing of this increase in the colourless elements which ulti- 
mately always refers us to an increased development of 
lymph-corpuscles within the irritated glands. 

It is now of importance that I should point out to you, 
that at present our conceptions concerning lymphatic 
glands are much more comprehensive than they were a 
short time ago. The most recent histological investiga- 
tions have shown that, in addition to the ordinary well- 








LYMPHOID ORGANS. 997 


known lymphatic glands, which are of a certain size, a 
great number of smaller apparatuses exist in the body 
which possess precisely the same structure, but do not 
exhibit such a complex arrangement as we find in a 
lymphatic gland. ‘To this class belong above all the fol- 
licles of the intestines, both the solitary and the Peyerian. 
A Peyer’s patch is nothing more than a lymphatic gland 
spread out as it were upon the surface ; the individual 
follicles of the patch, just as the solitary follicles of the 
digestive tract, correspond to the individual follicles of a 
lymphatic gland, only that the former, in man at least, 
are disposed in a single layer, the latter in several. The 
solitary and Peyerian glands have therefore nothing at 
all in common with the ordinary glands which pour their 
secretions into the intestinal canal ; on the contrary, they 
rather hold the position, and manifestly also fulfil the 
functions, of lymphatic glands. | 

To the same category belong in all probability also 
the analogous apparatuses which we find grouped to- 
gether in such large masses in the upper part of the 
digestive tract, where they form the tonsz/s and the folli- 
cles of the root of the tongue. Whilst in the intestine the 
follicles lie spread out on an even surface, in these parts 
the surface is inverted and the individual follicles lie 
around the involuted membrane. 

To the same category belongs moreover the thymus 
gland, which in its interior exhibits no other differences 
of structure excepting that the aggregation of the folli- 
cles reaches a still higher degree than in the lymphatic 
glands. Whilst in most of the lymphatic glands we have 
a hilus, where there are no follicles, this ceases to be the 
case in the thymus gland which has no hilus. 

Finally, to the same class belongs also a very essential 
constituent of the spleen, namely, the Malpighian or white 
bodies, which in different persons are distributed in just 


228 LECTURE IX. 


as different numbers throughout the parenchyma of the 
spleen, as the solitary and Peyerian follicles in the intes- 
tine. In a section through the spleen we see the trabe- 
cule radiating from the hilus towards the capsule and 
enclosing certain districts of glandular substance, within 
which the red spleen pulp lies, interrupted here and there 
by a sometimes greater, sometimes less, number of white 
bodies (follicles) of larger or smaller size, single or in 
groups, and sometimes almost clustered. The structure 
of these follicles agrees exactly with that of the follicles 
of lymphatic glands. 

We may therefore regard this whole series of appara- 
tuses as nearly equivalent to the lymphatic glands pro- 
perly so called, and a swelling of the spleen will, under 
certain circumstances, furnish just as abundant a supply 
of colourless blood-corpuscles, as is the case when a 
lymphatic gland enlarges. This possibility explains how 
it is that, for example, in cholera, where the change in 
the solitary glands and Peyer’s patches forms the chief 
part of the disease, and where the swelling of the other 
lymphatic glands is much less marked, we meet at an 
extremely early period with a considerable increase in 
the colourless corpuscles. Hereby is explained moreover 
why, in such cases of pneumonia as are connected with 
great swelling of the bronchial glands, an increase in the 
number of colourless blood-corpuscles likewise takes 
place, which is generally wanting in those forms of pneu- 
monia which are not connected with such swelling. The 
more the irritation extends from the lung to the lymph- 
atic glands, the more abundantly noxious fluids are con- 
veyed from the lung to the glands—the more manifestly 
does the blood undergo this change. 

Upon examining these different pathological processes 
in this manner one by one, it is really impossible to dis- 
cover anything at all, which in a morphological point of 


4 


REFUTATION OF A MORPHOLOGICAL PY AMIA. 229 


view, could even in a remote degree justify the assump- 
tion of a condition such as might be called pyeemia. In 
the extremely rare cases, in which pus breaks through 
into veins, purulent ingredients may, without doubt, be 
conveyed into the blood, but in such instances the intro- 
duction of pus occurs for the most part but once. The 
abscess empties itself, and if it be large, an extravasation 
of blood is more apt to ensue than the establishment of a 
persistent pyzmia. Perhaps we shall at some future 
time succeed, in the course of such a process, in discover- 
ing pus-corpuscles with well-defined characters in the 
blood ; at present, however, the matter stands thus, that 
it can most positively be maintained that nobody has hith- 
erto succeeded in demonstrating, by arguments capable 
of supporting even gentle criticism, the existence of a 
morphological pyemia. This name therefore must, as 
designating a definite change in the blood, be entirely 
abandoned. 


gs ht Oa A Oe os ae 


MARCH 17, 1858. 
METASTATICAL DYSCRASLA. 


Pyemia and phlebitis—Thrombosis—Puriform softening of thrombi—True and false 
phlebitis—Purulent cysts of the heart. 

Embolia—Import of prolonged thrombi—Pulmonary metastases—Crumbling away 
of the emboli—Varying character of the metastases—Endocarditis and capillary 
embolia—Latent pyemia. 

Infectant fluids—Diseases of the lymphatic apparatuses and secreting organs— 
Chemical substances in the blood; salts of silver—Arthritis—Calcareous metas- 
tases—Diffuse metastatic processes—Ichorrhemia—Pyemia asa collective name. 

Chemical dyscrasie—Malignant tumours, especially cancer—Diffusion by means of 
contagious parenchymatous juices. 


GENTLEMEN,—I was interrupted the last time in my 
description of pyeemia by the termination of the lecture, 
just as I was about to discuss the nature of the connection 
between this disease and certain affections of the vessels. 

As soon as it was found necessary to abandon the ori- 
ginal view, in accordance with which the mass of pus 
which was believed to be seen in a vein, was considered 
to have made its way in (been absorbed) through an 
opening in its walls, or through its yawning extremity, 
recourse was had to the doctrine of phlebitis, which is 
still the one most current. It was imagined that the pus 
which was regarded as the really noxious matter, was 


furnished as a product of secretion by the wall of the 
23u ; 


PHLEBITIS. 231 


vessel (John Hunter). This doctrine, however, presented 
some difficulty, because it was soon pretty generally 
allowed that a primary purulent inflammation of the veins 
did not occur, but that, as was first distinctly shown by 
Cruveilhier, at the commencement a clot of blood is 
always present. Cruveilhier himself was so greatly sur- 
prised at this observation of his, that he connected a the- 
ory with it which was beyond all medical comprehension. 
He concluded namely from the impossibility of explain- 
ing why inflammations of the veins began with coagula- 
tion of the blood, that inflammation in every case what- 
ever consisted in a coagulation of the blood. The impos- 
sibility of explaining phlebitis seemed to him to be got 
over by raising coagulation into a general law, and by 
referring every inflammation to a phlebitis on a small 
scale (capillary phlebitis). Cruveilhier was the more in- 
duced to assert this in consequence of his entertaining 
similar views with regard to other morbid processes, and 
believing that cysts, tubercles, cancer, and in short all 
important processes, accompanied by changes susceptible 
of anatomical demonstration, really ran their course 
within special, minute veins imagined by him. This man- 
ner of thinking, however, continued so entirely alien to 
that of the great majority of learned and unlearned phy- 
sicians, that the separate conclusions propounded by Cru- 
veilhier, which were‘adopted in medical science in part 
as drawn up by him, were altogether misunderstood. 
Cruveilhier was right in this point, as indeed has since 
been more and more acknowledged, namely, that the so- 
called pus in the veins in the first instance never lies 
against the wall of the vein, but always first appears in 
the centre of the previously existing clot of blood which 
marks the outset of the process. He imagined that the 
pus was secreted from the wall of the vessel, but that it 
did not remain there, but by means of “ capillary attrac- 


239 LECTURE X. 


tion” made its way to the centre of the clot. This was 
a very singular theory, which can only be approxima- 
tively comprehended by assuming, as it was still the cus- 
tom to do in Cruveilhier’s time, pus to be a simple fluid. 
But apart from these extremely obscure interpretations, 
the fact remains constant, against which even now no 
argument can be advanced, that 
before a trace of inflammation 
is visible, we find a clot, and 
that shortly afterwards in the 
middle of this clot a mass dis- | 


uk 






po 





“= al plays itself, which differs in ap- 
| Al , pearance from the clot, whilst 
, i on the other hand it exhibits a 
[: ‘Z| — greater or less resemblance to 
LE 2a! pus. 

inn With this observation as my 
| [_ A starting point, I have endea- 


voured to clear up the doctrine 
of phlebitis, as far as lies in my 
power, by substituting for the 
mysticism which pervaded Cru- 
veilhier’s interpretation, merely a statement of the real 
facts. We do not know that inflammation as such has 
any necessary connection with coagula ; on the contrary, 
it has turned out that the doctrine of stasis rests upon 
manifold misinterpretations. Inflammation may un- 
questionably exist when the current of blood within the 
vessels of the affected part is perfectly free and unob- 
structed. If we therefore leave inflammation on one 
side and confine our attention simply to the cegagulation 





Fig. 69. Thrombosis of the saphenous vein. S. Saphenous vein. 7. Thrombus: 
v, v’ thrombi seated on the valves (valvular) in process of softening, and connected 
by more recent and thinner portions of coagulum. C. Prolongation of the plug, 
projecting beyond the mouth of the vessel into the femoral vein C’. 


PURIFORM SOFTENING OF THROMBI. 933 


of the blood, to the formation of the clot (thrombus), it 
seems most convenient to comprehend the whole of this 
process under the term Thrombosis. I have proposed to 
substitute this term for the different names, phlebitis, ar- 
teritis, etc., inasmuch as the affection essentially consists 
in a real coagulation of the blood at a certain fixed spot. 
Upon investigating the history of these thrombi, we 
find that the puriform mass which is met with in their 
interior does not originate in the wall, but is produced 
by a direct transformation of the central layers of the 
‘clots themselves, a transformation indeed which is of a 
chemical nature, and during which, with a result similar 
to that which can be artificially obtained by the slow 
digestion of coagulated fibrine, the fibrine breaks up into 
a finely granular substance and the whole mass becomes 
converted into débris. This is a kind of softening and 
retrograde metamorphosis of the organic substance, in 
the course of which from the very commencement a num- 
ber of extremely minute particles 
become visible ; the large threads 
of fibrine crumble into pieces, these 
again into smaller ones, and so on 
until after a certain time has 
elapsed the chief part of the mass 
is found to be composed of small, 
‘fine, pale granules (Fig. 70, A). 
In cases in which the fibrine is 
comparatively very pure, we frequently see scarcely 
anything else than these granules. 





Fig. 70. Puriform mass of débris from softened thrombi. A. The granules seen 
in disintegrating fibrine, varying in size, and pale. 2B. The colourless blood-cor- 
puscles set free by the softening, some of them in process of retrograde metamor- 
phosis; a, with multiple nuclei, 6, with simple, angular nuclei and a few fat-gra- 
nules, c, non-nucleated (pyoid) corpuscles, in a state of fatty metamorphosis. (0. 
Red blood-corpuscles undergoing decolorization and disorganization, 350 diame- 


ters. 


234 LECTURE X. 


You see, gentlemen, the microscope solves the difficul- 
ties in a very simple manner, by demonstrating that this 
mass, which looks like pus, is not pus. For we under- 
stand by pus a fluid essentially provided with cellular 
elements. Just as little as we can imagine blood with- 
out blood-corpuscles, just as little can pus exist without 
pus corpuscles. But when, as in the present instance, 
we find a fluid which is nothing more than a mass per- 
vaded by granules, this may indeed, as far as external 
appearance goes, look like pus, but never ought to be 
regarded as real pus. Jt as a puriform, but not a puru- 
lent substance. 

But now we frequently see that in addition to these gra- 
nules a certain proportion of other structures show them- 
selves, for example, really cellular elements (Fig. 70, B), 
which are round (spherical), or angular, present one, two, 
or more nuclei, frequently le tolerably close to one an- 
other, and in reality exhibit a great similarity to pus- 
corpuscles, the distinction at most being that very often 
fat-granules occur in them, indicating that a process of 
disintegration is goingon. Whilst therefore in individual 
cases there can, on account of the often very greatly pre- 
ponderating mass of débris, exist no doubt as to what the 
observer has before him, in others considerable doubts 
may exist as to whether real pus is not present. These 
doubts cannot be removed in any other way than by an 
examination into the history of the development of the 
puriform mass. Now that we have already seen that 
colourless blood- and pus-corpuscles perfectly agree with 
one another in form, so that it is impossible to draw a 
real distinction between them, the question which sug- 
gests itself in cases where we find round, colourless cells 
in a clot of blood, whether these cells are colourless 
blood- or pus-corpuscles, can only be decided by deter- 
mining whether the corpuscles were present in the 








DISAPPEARANCE OF RED CORPUSCLES IN THROMBI. 9385 


thrombus from its very commencement, or only sprang 
up in it afterwards, or found their way into it in some 
other manner. Now upon accurately following up the 
different stages of the process, the very positive result is 
obtained that the corpuscles pre-exist, and that they do 
not arise within the clot, and are not forced into it. Even 
when quite recent thrombi are examined, the corpuscles 
are found in many places heaped up in great masses, so 
that, when the fibrine breaks up, they are set free in such 
numbers, that the débris are nearly as rich in cells as pus. 

It is with this process just as when water which is tho- 
* roughly impregnated with solid particles is frozen and 
then exposed to a higher temperature ; when the ice 


melts the enclosed particles must of course again come to 
light. 


To this view of the matter one objection may be raised, 
to wit, that we do not see the red blood-corpuscles set 
free in a similar manner. The red corpuscles, however, 
perish very early ; they are soon seen to grow pale ; they 
lose a portion of their colouring matter and become 
smaller, whilst numerous dark granules appear at their 
circumference (Figs. 54, a; 70, C), and in the majority 
of cases they entirely disappear, nothing but these gra- 
nules at last remaining. Still there are also cases in 
which the red corpuscles retain their integrity within the 
softening mass. As a rule they certainly perish, and it 
is precisely upon this that depends the peculiarity of the 
transformation, by means of which a yellowish white 
fluid arises bearing the external appearance of pus. And 
for it too an explanation may be found without any par- 
ticular difficulty, if it be borne in mind how very trifling 
is the power possessed by the red blood-corpuscles of 
resisting the most various reagents. If to a drop of 
blood you add a drop of water, you see the red corpus- 


236 LECTURE X. 


cles disappear before your eyes while the colourless ones 
remain behind. 

That therefore, which according to the ordinary nomen- 
clature is called suppurative phlebitis, is neither suppu- 
rative, nor yet phlebitis, but a process which begins with 
a coagulation, with the formation of a thrombus in the 
blood, and afterwards presents a stage in which the 
thrombi soften, so that the whole history of the process 
is contained in the history of the thrombus. But here I 
must impress upon you that I do not, as has been said of 
me in different quarters, deny the possibility of a real 
phlebitis, and that I have not in any way discovered that 
there is no such thing as phlebitis. No/ phlebitis cer- 
tainly does exist. But it is an inflammation which really 
affects the walls, and not the contents of a vessel. In 
the larger vessels the most different layers of their walls 
may become inflamed and enter upon every possible 
phase of inflammation, and yet all the while their chan- 
nel remain entirely unaltered. In accordance with the 
views generally entertained the internal coat of the ves- 
sels was thought to be like a serous membrane, and as 
this readily furnishes fibrinous exudations or purulent 
masses, the same was supposed to be the case with the 
internal coat. Concerning this point a series of investi- 
gations was years ago set on foot, and I too have occu- 
pied myself at various times with it, but hitherto no ex- 
perimenter, who carefully prevented the blood from 
streaming into the vessels, has succeeded in producing an 
exudation, which was deposited in their cavity. On the 
contrary, when the wall is inflamed, the ‘‘exuded mat- 
ter” (Exsudatmasse) passes into the wall, which becomes 
thicker, cloudy, and subsequently begins to suppurate. 
Nay, even abscesses may form, which cause the wall to 
bulge on both sides like a variolous pustule, without any 
coagulation of the blood ensuing in the cavity of the ves- 


PURULENT CYSTS IN THE HEART. 237 


sel. At other times, certainly, phlebitis, properly so 
called (and in like manner arteritis and endocarditis), is 
the cause of thrombosis, in consequence of the formation 
of inequalities, elevations, depressions, and even ulcera- 
tions upon the inner wall which favour the production of 
the thrombus. Still, wherever phlebitis, in the usual 
sense of the word, takes place, the alteration in the coat 
of the vessel is almost always a secondary one, and in- ~ 
deed occurs at a comparatively late period. 

The process runs its course in such a way that the most 
recent parts of the thrombus always consist of the blood 
which has most lately coagulated. The softening, the 
partial liquefaction, generally commences in the centre, 
in the oldest layers, so that, when the thrombus has 
attained a certain size, there exists in the midst of it a 
cavity of larger or smaller dimensions, which gradually 
enlarges and keeps approaching more and more closely 
to the wall of the vessel. But in general this cavity is 
shut off in an upward and downward direction by means 
of a more recent and tougher portion of the clot which, 
after the manner of a cap, takes care that, as Cruveilhier 
expresses himself, the ‘‘ pus” remains sequestered, 
and all contact between the dédris and the circulating 
blood is prevented. Only sideways does the softening 
extend until it at last reaches the wall of the vessel itself ; 
this becomes altered, it begins to grow thicker and at 
_ the same time cloudy, and ultimately even suppuration 

takes place within the walls. 

The same thing which we have hitherto considered in 
the veins occurs alsoin the heart. In the right ventricle 
especially we not unfrequently see what are called puru- 
lent cysts between the trabecule of its wall. They pro- 
ject into the cavity like small rounded knobs, and form 
little pouches which, when cut open, contain a soft pulp © 
that may present a completely pus-like appearance. 


238 LECTURE X. 


People have plagued themselves to an indefinite extent 
about these purulent cysts and invented all possible the- 
ories to account for them, until at length the simple fact 
came out, that their contents are frequently nothing 
more than a finely granular pulp of an albuminous sub- 
stance, which does not offer even the slightest resem- 
blance in its more intimate structure to pus. This was 
so far tranquillizing, as there is no observation as yet on 
record of the death of any patient from pyszemia who had 
sacs of this description even in pretty considerable num- 
ber, but it ought to have struck those who are so much in- 
clined to establish a connection between peripheral throm- 
boses, which are however just the same thing, and pyaemia. 

For the question naturally arises how far particular 
disturbances that can be designated by the name of pyx- 
mia may, in consequence of the softening of the thrombi, 
be evoked in the body. To this in the first place we may 
answer that secondary disturbances certainly are very 
frequently occasioned, but not so much by the immediate 
introduction of the softened masses as fast as they be- 
come liquid into the blood, as by the detachment of lar- 
ger or smaller fragments from the end of the softening 
thrombus which are carried along by the current of blood 
and driven into remote vessels. This gives rise to the 
very frequent process upon which I have bestowed the 
name of E’mbola. 

This is an occurrence which we can here only briefly 
touch upon. In the peripheral veins the danger pro- 
ceeds chiefly from the small branches. By no means 
rarely do these become quite filled with masses of coagu- 
lum. As long however as the thrombus is confined to 
the branch itself, so long the body is not exposed to any 
particular danger ; the worst that can happen is that, in 
consequence of a peri- or meso-phlebitis,* an abscess 


* See the Author’s ‘“ Gesammelte Abhandl.,” p. 484. 


EMBOLIA—PROLONGED THROMBI AND THEIR IMPORT. 239 


may form and open externally. Only the greater num- 
ber of the thrombi in the small branches do not. content 
themselves with advancing up to the level of the main 
trunk, but pretty constantly new masses of coagulum de- 
posit themselves from the blood upon the end of the 
thrombus layer after layer, the thrombus is prolonged 
beyond the mouth of the branch into the trunk in the 
direction of the current of the blood, shoots out in the 
form of a thick cylinder farther and farther, and becomes 
continually larger and larger. Soon this prolonged 
thrombus (Fig. 71, ¢) no longer bears any proportion to 
the original (autochthonous) thrombus (Fig. 71, c), from 
which it proceeded. The prolonged thrombus may have 
the thickness of a thumb, the original one that of a knit- 
ting-needle. From a lumbar vein, for example, a plug 
may extend into the vena cava as thick as the last pha- 
lanx of the thumb. 











It is these prolonged plugs that constitute the source 
of real danger ; it is in them that ensues the crumbling 
away which leads to secondary occlusions in remote ves- 
sels. They are the parts from which larger or smaller 


Fig. 71. Autochthonous and prolonged thrombi. ¢, c’. Smallish, varicose, lateral 
branches (circumflex veins of the thigh), filled with autochthonous thrombi which 
project beyond the orifices into the trunk of the femoral vein. ¢. Prolonged 
thrombus produced by concentrically apposed deposits from the blood. ?¢. Pro- 
longed thrombus, as it appears after fragments (emboli) have become detached from 
it. 


240 LECTURE X. 


particles are torn away by the blood as it streams by - 
(Hig h, ¢). 

Through the vessel originally occluded no blood at all 
flows ; in it the circulation is entirely interrupted : but 
in the larger trunk through which the blood still con-— 
tinues its course, and into which only at intervals the 
thrombus-plugs project, the stream of blood may detach 
minute particles, hurry them away with it, and wedge 
them tightly into the nearest system of arteries or capil- 
laries. | 

Thus we see, that as a rule all the thrombi at the pe- 
riphery of the body produce secondary obstructions and 
metastatic deposits in the lungs. I long entertained 
doubts whether I ought to consider the metastatic inflam- 
mations of the lungs one and all as embolical, because it 
is very difficult to examine the vessels in the small me- 
tastatic deposits, but I am continually becoming more 
and more convinced of the necessity of regarding this 
mode of origin as the rule. When a considerable num- 
ber of cases are compared statistically, the result ob- 
tained is that every time metastatic deposits occur, 
thrombosis is also present in certain vessels. Quite re- 
cently, for example, we have had a tolerably severe 
epidemic of puerperal fever, and in this it was found 
that, however manifold the forms the disease assumed, 
yet all those cases which were accompanied by metas- 
tases in the lungs, were also attended with thrombosis in 
the region of the pelvis or in the lower extremities, whilst 
in the inflammations of lymphatic vessels the pulmonary 
metastases were wanting. Such statistical results carry 
with them a certain amount of compulsory conviction, 
even where strict anatomical proof is wanting. 

Into the pulmonary artery the introduced fragments of 
thrombus of course penetrate to different depths accord- 
ing to their size. Usually a fragment of the kind sticks 








DIFFERENT VARIETIES OF METASTATIC DEPOSITS. 941 


- fast where a division of the vessel takes place (Fig. 72, Z), 
because the diverging vessels are too small to admit it. 
In the case of very large fragments even 
the principal trunks of the pulmonary 
artery are blocked up, and instantaneous 
asphyxia ensues ; other fragments again 
penetrate into the most minute arteries 
and there give rise to very minute, and 
sometimes miliary inflammations of the 
parenchyma. In explanation of these 
small and often very numerous deposits, 
I must mention a conjecture which only 
occurred to me whilst engaged in my more recent 
observations, but which I-do not scruple to declare to be 
a necessary inference. I believe namely that,-when a 
considerable fragment of a thrombus becomes wedged at 
a certain point in an artery, it may in its turn crumble 
away through the onward pressure of the blood, and thus 
the minute particles to which this crumbling of the lar- 
ger plug gives rise be conveyed into the small branches 
into which the vessel breaks up. Thus alone does it 
seem to me that the fact can be explained, that in the 
district supplied by an artery of considerable size a num- 
ber of little deposits of the same sort are often found. 
This whole series of cases has nothing whatever to do 
with the question, whether there is pus in the blood or 
not. We have in them to deal with bodies of quite a 
different nature, with fragments of coagula in a more or 
less altered condition, and according as this alteration 
has assumed this or that character, the nature of the pro- 


Fie. 72. 





Fig. 72. Embolia of the pulmonary artery. P. Moderately large branch of the 
pulmonary artery. 2. The embolus, astride upon the angle (spur—Sporn), formed 
by the division of the artery. ¢, ¢’. The capsulating (secondary) thrombus: #¢, the 
portion in front of the embolus reaching to the next highest collateral vessel ¢ ; 
t’, the portion behind the embolus, in a great measure filling up the diverging 
branches 7, r’, and ultimately terminating in the form of a cone. 


16 


949, LECTURE X. 


cesses which arise in consequence of the obstruction may 
also be very different. If, for example, a gangrenous 
softening has taken place at the original site of the coa- 
gulum, the metastatic deposit will also assume a gangre- 
nous character, just as this would be the case if gangre- | 
nous matter were inoculated. So, wece versd, it also 
happens that the secondary disturbances, like those at 
the spot whence the fragments were detached, run a very 
favourable course, the embolus like the thrombus becom- 
ing converted into pigment and connective tissue, and at 
the same time growing smaller. 

This group of processes must be separated from those 
ordinarily occurring in pyzemia all the more, because the 
same processes are also met with on the other side of the 


Rie. 73: 





lungs in the regions belonging to the left side of the cir- 
culation, where they often run the same course and pre- 


Fig. 78. Ulcerative endocarditis affecting the mitral valve. a. The free, smooth 
surface of the mitral valve, beneath which the connective-tissue-corpuscles are en- 
larged and clouded, whilst the intervening tissue is denser than usual. 6. A con- 
siderable hilly swelling caused by increasing enlargement and cloudiness of the tis- 
sue. c. A swollen part which has already begun to softenand break up. d,d. The 
tissue at the lower part of the valves which is stil but little altered, with numerous 
corpuscles, the results of proliferation. e, e. The commencement of the enlarge- 
ment, cloudiness, and proliferation of the corpuscles. 80 diameters. 











CAPILLARY EMBOLIA. 943 


sent the same results, but are still less dependent upon 
an original phlebitis. Thus, for example, endocarditis 
by no means seldom forms the starting point of such me- 
tastases. Ulceration takes place in one of the valves of 
the heart, not by means of the formation of pus, but in 
consequence of an acute or chronic softening ; crumbling 
fragments of the surface of the valve are borne away by 


‘the stream of blood and reach with it far distant points. 


The kind of obstruction which these masses produce is 
altogether similar to that which the thrombi in the veins 
give rise to, but they present a different chemical consti- 
tution. Their minuteness also and their friability favour 
their penetration into the smallest vessels in a high de- 
gree. Therefore we do not so very unfrequently find 
the obstructing mass in minute microscopical vessels 


Fig. 74. Fie. 75. 





Fig. 74—75. Capillary embolia in the tufts (penicilli) of the splenic artery after 
endocarditis (Cf. Gesammelte Abhandlungen zur wiss. Medicin. 1856, p. 716). 
74. Vessels of a tuft magnified 10 times, in order to show the position of the oc- 
cluding emboli in the arterial district. 75, An artery filled a little before its divi- 
sion, and in the branches into which it next divides, with fragments of the finely 
granular embolic mass (Cf. Fig. 73, ¢). 300 diameters. 


244. LECTURE X. 


which are no longer to be followed with the naked eye, 
and in them it usually extends as far down as a point of 
division and somewhat beyond. This mass constantly 
presents a finely granular appearance, and does not con- 
sist of the coarse débris that we find in the veins, but of 
a very fine, yet at the same time dense, granular matter ; 
chemically, it possesses the extremely convenient quality 
for examination of being remarkably resistant to the ordi- 
nary tests, and thus readily distinguished from other mat- 
ters. This is capillary embolia properly so called, one of 
the most important forms of metastasis, which frequently 
gives rise to minute deposits in the kidney, the spleen, 
and the substance of the heart itself; in certain cases 
occasions sudden occlusions in the vessels of the eye or 
brain, and according to circumstancs produces metastatic 
deposits or sudden functional disturbances (amaurosis, 
apoplexy). Here too one can clearly convince oneself 
that in recent cases the wall of the vessel is quite unal- 
tered at the seat of the affection ; nay here indeed the 
doctrine of phlebitis would no longer suffice, since these 
are not vessels which possess vasa vasorum, and concern- 
ing which it might be assumed that a secretion proceeded 
from the wall inwards. In these cases it is impossible to 
regard the occluding mass in any other light than as one 
primarily existing in the vessel, and in no wise depend- 
ent upon the condition of its wall. 

Perhaps this description has convinced you, gentlemen, 
that two essential errors have existed in the doctrine of 
pyemia ; the one, that people thought they had found 
pus-corpuscles in the blood, when only colourless blood- 
corpuscles were really present ; the second, that they 
thought they had found pus in vessels in which nothing 
more than the products of the softening of fibrine existed. 
Yet we have ascertained that this last class of cases cer- 
tainly furnishes the most important source of genuine 








METASTASES DUE TO INFECTANT MATTERS, 945 


metastatic deposits. But in my opinion, the history of 
the processes which have been called pyzemia is not con- 
fined to these conditions. When the process runs its 
course free from all complication, so that from the origi- 
nal seat of the disease (thrombosis in a vein, endocarditis, 
etc.), only so/éd masses in an undecomposed state are de- 
tached and cause obstructions, the real process is in 
many cases brought to notice only in consequence of the 
metastasis. There are cases which run their course so 
latently that all the earlier stages of the affection are en- 
tirely overlooked, and that the first rigors which declare 
themselves announce that the development of the meta- 
static processes has already set in. Usually, however, 
another condition must be taken into consideration, 
which is not directly accessible either to the coarser or 
more delicate modes of anatomical investigation ; I mean 
certain fluids, which in themselves bear no immediate and 
necessary relation to pus as such, but manifestly differ 
very much from one another in their nature and origin. 
Whilst I was engaged in the consideration of the 
changes which lymph undergoes, I pointed out to you 
(p. 220), that fluids which were taken up by lymphatic 
vessels were not only freed in the filters of the lymphatic 
glands from. corpuscular elements, but were also in part 
attracted and retained by the substance of the glands, so 
as to display some activity within them. Similar effects 
appear to take place also. elsewhere than in the glands. 
Where the reabsorption was primarily effected by the 
veins, this must, of course, always be the case. There is 
namely a series of peculiar phenomena which pervade all 
infectious processes as a constant element. These are 
on the one hand the changes which the lymphatic and 
lymphoid glands may undergo not so much at the 
seat of the primary affection as rather in the body gene- , 
rally, and on the other hand the changes which the 


246 LECTURE X. 


secreting organs offer, through which the matters have 
to be excreted. 

It was for some time believed that twmefaction of the 
spleen was characteristic of typhoid fever, inasmuch as it 
formed a parallel to the swellings of the mesenteric 
glands occurring in that disease. But more accurate 
observation has shown that a great number of feverish 
conditions which follow a more or less typhoid course, 
and affect the nervous system in such a manner that a 
state of depression is brought about in its most important 
central organs, set in with swelling of the spleen. The 
spleen is a remarkably sensitive organ, which swells not 
only in intermittent and typhoid fever, but also in 
most other processes in which noxious, infectant matters 
have been freely taken up into the blood. No doubt the 
spleen must always be considered in its near relationship 
to the lymphatic system, but its diseases in addition usu- 
ally bear a very direct relation to analogous diseases of 
the important glands in its vicinity, especially the liver 
and the kidneys. In most cases of infection do these 
three organs exhibit corresponding enlargement con- 
nected with real changes in their interior ; but since these 
changes do not, even on microscopical examination, ap- 
parently present anything remarkable, the attention of 
the observer is chiefly attracted by the result which is 
obvious to the naked eye, namely, the great swelling. 
On careful comparison, however, a good deal is disco- 
vered, so that we can affirm with certainty that the gland- 
cells quickly become changed, and that disturbances 
early show themselves in the elements by means of which 
the secretion is to be accomplished. I shall revert to 
this subject hereafter. Allow me now, in elucidation of 
these conditions, in the first place to advert to one or two 
more obvious examples which are accessible to direct 
observation. 





DEPOSITION OF SILVER IN THE TISSUES, QAT 


We know that.when any one takes salts of silver, they 
penetrate into the different tissues of his body ; and if we 
do not employ them in a really corrosive and destructive 
manner, the silver penetrates into the elements of the 
tissues in a state of combination, the nature of which has 
not yet been satisfactorily made out, and, when it has 
been made use of long enough, produces a change of 
colour at the point of application. A patient who had 
in Dr. Von Graefe’s out-patient room on the 10th No- 
vember received a solution of nitrate of silver as a lotion, 
very conscientiously employed the remedy up to the pre- 
sent time (17th March) ; the result of which was that his 
conjunctiva assumed an intensely brown, nearly black 
appearance. The examination of a piece cut out of it 
showed that silver had been taken up into. the paren- 
chyma, and indeed in such a manner that the whole of 
the connective tissue had a slightly yellowish brown hue 
upon the surface, whilst in the deeper parts the deposi- 
tion had only taken place in the fine elastic fibres of the 
connective tissue, the intervening parts, the proper basis- 
substance, being perfectly free. But deposits of an en- 
tirely similar nature take place also in more remote 
organs. Our collection contains a very rare preparation 
from the kidneys of a person who on account of epilepsy 
had long taken nitrate of silver internally. Init may be 
seen the Malpighian bodies, in which the real secretion 
takes place, a blackish blue colouring of the whole of the 
membrane of the coils of the vessels, limited to this part 
in the cortex, and appearing again, in a similar, though 
less marked form, only in- the intertubular stroma of the 
medullary substance. In the whole kidney, therefore, 
besides the parts which constitute the real seat of their 
secretion, those only are altered which correspond to the 
ultimate system of capillaries in the medullary substance. 


248 LECTURE X. 


Of the well-known discoloration of the skin by silver I 
need not speak here. 

Another instance is afforded us by gout. If we exa- 
- mine the concretions (tophi) in the joints of a gouty per- 
son, we find they are composed of very delicate, needle- 
shaped, crystalline deposits of all possible sizes, and con- 
sisting of urate of soda, with at most here and there a 
pus- or blood-corpuscle lying between them. We have 
here therefore also, as when silver has been employed, 
to deal with a material substance which is usually ex- 
creted by the kidneys, and that indeed not rarely in such 
large quantities, that deposits form even within the kid- 
ney itself and large crystals of urate of soda accumulate, 
especially in the uriniferous tubules of the medullary 
portion, so as sometimes to lead even to an occlusion of 
the tubules. If, however, this secretion does not pro- 
~ ceed in a regular manner, the immediate result 1s an ac-, 
cumulation of urates in the blood, as has been shown in 
a very able manner by Garrod. Then at last deposits 
begin to form at other points, not throughout the whole 


body, nor uniformly in all parts, but at certain definite 
points and in accordance with certain rules. 


Here we have to do with very different forms of meta- 
stasis from those with which we became acquainted 
whilst considering the nature of embolia. That the | 
changes which ensue in the substance of the kidney, in 
consequence of the absorption of silver from the stomach. 
accord with what has in pathology since times of old 
been termed metastasis is unquestionable. This consists 
in a transferrence of matter from one spot to another, so 
that the same substance which had previously been pre- 
sent in the first comes and lodges in the second, and the 
secreting organ takes up minute particles of the matter 
into its own tissue. This is what we find constantly 


METASTASIS. 249 


recurring in the history of all metastatic deposits of this 
kind, in which only matters in solution and not particles of 
a visible and mechanical nature are present in the blood. 
The urate of soda cannot be directly seen in the blood 
of the gouty person, unless it have previously been col- — 
lected by the help of chemical processes ; and just as lit- 
tle the salts of silver. | 

I have moreover described a new form of metastasis 
which is certainly more rare but yet belongs to the same 
category. When calcareous salts are reabsorbed from the 
bones in large quantity, the bone-earth is generally ex- 
creted by the kidneys, likewise in large quantity, so that 
sediments form in the urine, the knowledge of which has 
straggled down to us in the history of osteomalacia 
[mollities ossium], from the notorious Mme. Supiot in 
the last century. But this regular excretion of the cal- 
_careous salts is not unfrequently impaired by disturb- 
ances in the functions of the kidneys, in the same way 
as in arthritis the-excretion of urate of soda; then there 
also arise metastatic deposits of bone-earth, but at other 
points, namely the lungs and the stomach. Considerable 
portions of the lungs sometimes become calcified without 
any injury to the permeability of the respiratory pas- 
sages ; the diseased parts look like fine bathing sponge. 
‘The mucous membrane of the stomach becomes filled in 
like manner with calcareous salts, so that it feels like a 
rasp and grates under the knife without the glands of the 
stomach becoming directly implicated ; they are merely 
imbedded in a stiffened mass, and possibly even thus 
secretion might take place from them. 

To these kinds of metastasis in which definite sub- 
stances, though not in a palpable form, but in solution, 
find their way into the mass of the blood, careful atten- 
tion must at all events be paid when we endeavour to 
unravel the complex mass of conditions which are com- 


950 LECTURE X. 


prehended under the term pyzemia. I see at least no other 
possible way of explaining certain more diffuse processes, 
which do not present themselves in the form of the ordi- 
nary circumscribed metastatic deposits. To this class be- 
longs that metastatic pleurisy which develops itself with- 
out any metastatic abscesses in the lungs—that seemingly 
rheumatic articular affection, in which no distinct deposit 
is found in the joints—that diffuse gangrenous inflamma- 
tion of the subcutaneous connective tissue which cannot 
well be accounted for unless we suppose a more chemical 
mode of infection. Here we have, as may be seen in 
cases of variolous and cadaveric infection, to deal with a 
transferrence of corrupted, wchorous juices into the body ; 
and we must admit the existence of a dyscrasia (¢chorous 
wnfection) in which this ichorous substance which has 
made its way into the body, displays its effects in an 
acute form in the organs which have a special predi- 
lection for such matters. : 

Now it may possibly happen that in the course of the 
same case of illness the three different changes which we 
have considered may coexist. An increase in the num- 
ber of the colourless corpuscles (leucocytosis) may take 
place to such an extent as to tempt one to believe in the 
presence of a morphological pyemia. This will at all 
events always be the case when the process has been con- 
nected with extensive irritation of the lymphatic glands. 
The formation of thrombi, moreover, and embolia with 
metastatic deposits may occur. And finally there may 
at the same time be taking place an absorption of icho- 
rous or putrid juices (ichorrhemia, septhemia). These 
three different conditions may present themselves as com- 
plications one of the other, but do not necessarily coin- 
cide. If it be wished therefore to retain the term pyex- 
mia, let it be reserved for such complications as these, 
only we must not seek for a common central point in a 


ICHORRHAMIA—CANCEROUS DYSCRASIA. 251 


purulent infection of the blood, but the term must be re- 
garded as a collective name for several processes dissimi- 
lar in their nature. 

I hope, gentlemen, that ae I have now imparted to 
you will be sufficient to put you in possession of the chief 
bearings of the subject. Of course no real demonstra- 
tion can be afforded without reference to distinct cases. 
You will, however, yourselves have sufficient opportunity 
for testing the exactitude of this description of mine, and 
I shall be glad if you find that important data have 
thereby also been furnished, by which clearer conceptions 
with regard to the really practical, and especially the 
therapeutical, questions arising out of the subject, may 
be obtained. 


Now that we have become acquainted not only with 
corporeal particles, but also with certain chemical sub- 
stances as the originators of dyscrasia, lasting for a lon- 
ger or shorter time according as the supply of these par- 
ticles and substances continues for a longer or shorter pe- 
riod, we may briefly revert to the question, whether, in 
addition to these forms, a kind of dyscrasia can be shown 
to exist in which the blood is the permanent seat of definite 
changes. We must answer this question in the negative. 
The more marked a really demonstrable contamination . 
of the blood with certain matters is, the more manifest 
is the relatively acute course of the process. Just the 
very forms* in which medical men are most apt to con- 
sole themselves—especially for the shortcomings of the 
therapeutical results, with the reflection that they have 
to do with the deeply rooted and incurable chronic dys- 
crasia—just these forms depend, I imagine, least of all 
upon an original change in the blood ; for these are pre- 


* Tubercle, cancer, purpura, syphilis, etc. 


259 LECTURE X. 


cisely the cases, in the majority of which extensive alte- 
rations are discovered in certain organs or in individual 
parts. I cannot assert that investigation has in this mat- 
ter in any way been pushed to its utmost limits, I can 
only say that every resource afforded by microscopical 
or chemical analysis has hitherto been fruitlessly em- 
ployed in investigating the part played by the blood in 
these processes ; and that, on the other hand, we are in 
most of them able to demonstrate important changes in 
larger or smaller groups of the ultimate constituents of 
organs ; and that on the whole the probability that the 
dyscrasia should in these instances also be regarded as 
secondary, and as derived from definite points in organs, 
becomes stronger every day. I shall have to examine 
this question a little more closely when J come to con- 
sider the theory of the propagation of malignant tumours, 
in the case of which recourse is, you know, so often had 
to the supposition that the malignancy has its root in the 
blood which gives rise to the local affections. And yet 
it is precisely in the course of these processes that it is 
comparatively most easy to show the mode of propaga- 
tion, both in the immediate neighbourhood of the dis- 
eased part, and in remote organs; and it is in them we 
find, that there is one circumstance which especially 
favours the extension of such processes, namely the 
abundance of parenchymatous juices in the pathological 
formation. The drier a new formation is, the less in 
general are its powers of infecting, both nearer and more 
distant parts. ‘T'he mode of propagation itself commonly 
entirely agrees with what we have already said ; first of 
all, a conveyance of the morbid matter though the 
lymphatic channels, and then an affection of the lymph- 
atic glands, takes place, and it is only by degrees that 
processes of a similar nature declare themselves in more 
remote organs. Or the process may here too in the first 


DIFFUSION BY MEANS OF CONTAGIOUS JUICES. 953 


instance encroach upon the walls of the veins, so that 
they become really cancerous, and after a certain time 
- the cancer either grows directly through the walls into 
the vessel and there continues its course, or a thrombus 
forms at the point, which invests the cancerous plug in 
a greater or less degree and into which the mass of can- 
cer grows. Here, therefore, we see a diffusion of the 
disease may possibly take place in two different manners, 
but the diffusion of corpuscular elements only in one, 
when, namely, an irruption ensues into the veins. An 
absorption of cancer-cells by means of the lymphatics 
cannot indeed in itself be ranked amongst impossibilities, 
but at all events this much is certain, that no propaga- 
tion of the disease can take place until the lymphatic 
glands have in their turn undergone a compléte cancer- 
ous transformation, and similar masses of cancer push on 
their growth from them into their efferent vessels. In 
no case can a peripheral lymphatic vessel sweep along 
into the blood the cells of the cancer so simply as it does 
the fluid parts ; this is only conceivable and possible in 
the case of the veins. But even in that case there is not 
the slightest probability that noxious matters are fre- 
quently diffused by their means, and for the simple rea- 
son that the metastases of cancer very frequently do not 
correspond with those with which we have become ac- 
quainted as occurring in embolia. The usual form of 
metastatic diffusion in cancer follows rather the direction 
of the secreting organs. The lungs, as is well known, are 
much more rarely invaded by cancerous disease than the 
liver, not only after gastric and uterine, but also after 
mammary cancer which would necessarily rather produce 
' cancer in the lungs, if it were anything corpuscular which 
was conveyed away, became stagnant and gave rise to a 
new eruption of the disease. The manner in which the 
metastatic diffusion takes place seems, on the contrary, 


254 LECTURE X. 


to render it probable that the transferrence takes place by 
means of certain fluids, and that these possess the power 
of producing an infection which disposes different parts 
to a reproduction of a mass of the same nature as the 
one which originally existed. We need only imagine a 
process similar to that which we see upon a large scale 
in small pox. The pus of small pox when directly ino- 
culated does indeed induce the disease, but the conta- 
gium™* is also volatile, and a person may have pustules 
over his skin after merely breathing air of a certain cha- 
racter. <A similar state of things seems to prevail in 
cases, in which, in the course of heteroplastic processes, 
dyscrasize occur which do not burst out afresh at points 
which, according to the direction of the current of blood 
or lymph, would be most directly exposed to them, but 
at remote spots. As the salts of silver do not deposit 
themselves in the lungs, but pass through them to be 
precipitated only when they reach the kidneys or the 
skin, so an ichorous juice may pass from a cancerous 
tumour through the lungs without producing any change 
in them, and yet at a more remote point, as for example 
in the bones of a far distant part, excite changes of a 
malignant nature. 


* 4. e. Contagious matter.— Transl, 








Laat ORE xT. 


MARCH 27, 1858, 
PIGMENTARY ELEMENTS IN THE BLOOD. NERVES. 


Melanemia—Its relation to melanotic tumours and colorations of the spleen. 

Red blood-corpuscles—Origin—Melanic forms—Chlorosis—Paralysis of the respira- 

tory substance—Toxiceemia. 

The nervous system—lIts pretended unity. 

Nerve-fibres—Peripheral nerves: their fasciculi, primitive fibres, and perineurium 
—Axis-cylinder (electrical substance)—Medullary substance (Myeline) Ne on- 
medullated and medullated fibres—Transition from the one kind to the other: 
hypertrophy of the optic nerve—Different breadth of the fibres—Their termina- 
tions—Pacinian and tactile bodies. 


GrnTLEMEN,—I have still some observations to make 
to you in reference to the changes of the. blood, more for 
the sake of completeness than because I am able to OneE 
to you in doing so any decisive points of view. 

In the first place I wish to mention one other condi- 
tion which has recently been a great deal talked about, 
and might, when occasion offered, present increased in- 
terest to you, the so-called melanemia. This is a condi- 
tion most nearly connected with leukemia, inasmuch we 
have in it to deal with elements, which, like the colour- 
less corpuscles in leukgeemia, make their way from defi- 
nite organs into the blood and circulate with it. The 
number of recorded observations concerning this matter 
is already tolerably large, indeed I might almost say, 

255 


256 LECTURE XI. 


larger than perhaps is necessary, for it seems indeed that 
here and there mistakés have slipped in, which should, I 
think, be again removed from the history of the affection. 
But unquestionably there is a state in which coloured 
elements are met with in the blood that do not belong to 
it. Isolated observations in support of this fact have 
already for a considerable length of time* been upon 
record, and indeed first occur in the history of melanotic 
tumours, concerning which it has frequently been de- 
clared that in their neighbourhood minute black particles 
are met with in the vessels, and the opinion put forward 
that from this source the melanotic dyscrasia arose. But 
this is not quite the condition which is meant when me- 
laneemia is now-a-days spoken of. In the last ten years 
not a single observation has been made known which in 
any way adds to our knowledge concerning the passage 
of the particles of melanotic tumours into the blood. 

The first observation concerning that class of diseases 
which in a narrower sense of the word is designated me- 
lanzemia, was made by Heinrich Meckel in the case of a 
lunatic a short time after I had published my description 
of leukemia. Meckel found that here too the spleen was 
enlarged in a very considerable degree and pervaded by 
black pigment, and he therefore ascribed the change in 
the blood to an absorption of coloured particles from the 
spleen. The next observation I made myself (and that 
too in a class of cases which afterwards proved very fruit- 
ful) in the case of an ague-patient, who had long been 
afflicted with a considerable enlargement of the spleen ; 
for I found in the blood of his heart cells containing pig- 
ment. Meckel had only observed free granules and 


* Dr. Stiebel, sen., of Frankfort-on-the-Maine, calls my attention to the fact. that 
he had already in a review of Schénlein’s Clinical Lectures (in Haser’s ‘ Archiv’), 
mentioned the occurr.nce of pigment-cells in the blood. 

Note to the Second Edition. 





MELAN MIA. O57 


flakes (Schollen) containing pigment. The cells which I 
discovered in many respects bore a resemblance to colour- 
less blood-corpuscles ; they were spherical, but frequently 
also rather oblong, nucleated cells, within which a 
greater or less number of large black granules were to 
be seen. In this case also the occurrence of a large black 
spleen was again verified. Since that time attention has 
been continually more and more drawn to 
these conditions by Meckel himself and 
@» by a number of other observers in Ger- 
> A +4 ¥\ many, and last of all by Frerichs, and 
| in Italy by Tigri. Tigri has not scrupled 
to designate the disease mlza nera, from 
the blackness of the spleen in it, whilst 
according to the view of Meckel which has been ex- 
panded by Frerichs, it is rather one of the more severe 
forms of intermittent fever which is to be explained in 
this way. 

It has been attempted to explain the serious import of" 
these affections by supposing that the elements, which 
find their way into the blood, accumulate at certain 
points in the more minute capillary districts, and there 





_ produce stagnation and destruction. This was especially 


held to be the case in the capillaries of the brain, in 
which they were said to attach themselves after the man- 
ner of emboli to the points of division, and so occasion 
sometimes capillary apoplexies, sometimes the comatose 
and apoplectic forms of severe intermittent fever. Fre- 
richs has added a new and important kind of obstruction, 


‘namely, that of the minute hepatic vessels, which is said 


ultimately to give rise to atrophy of the arent vind of 
the liver. 


Fig. 76. Melanemia. Blood from the right heart (Cf. ‘ Archiv f. pathol. Anato- 
mie und Physiologie,’ vol. ii., fig. 8, p. 594). Colourless cells of various shapes 
filled with black, and in part angular, pigment-granules, 800 diameters, 

17 


258 LECTURE XI. 


If all this be the case, there would seem to exist an 
extremely important series of conditions directly depend- 
ent upon the dyscrasia. Unfortunately I can myself say 
but little concerning the matter, inasmuch as I have not 
since my first case again been in a position to observe 
anything similar. I cannot therefore form a decided 
opinion with regard to the value of the relations which 
have been laid down with respect to the connection of 
the secondary changes with the contamination of the 


blood. I only wish to remark that all the facts with 
which we are acquainted concerning these conditions, in 
dicate that the contamination of the blood has its rise in 
a definite organ, and that this organ, asin the case of the 
colourless blood-corpuscles, is generally the spleen. 


In the course of my description of the blood I have 
hitherto scarcely made any mention of the changes which 
take place in the red corpuscles, not by any means be- 
cause I regarded them as unimportant constituents of 
that fluid, but because as yet remarkably little is known 
concerning their changes. The whole history of the red 
blood-corpuscles is still invested with a mysterious obscu- 
rity, Inasmuch as no positive information has even at the 
present time been obtained with regard to the origin of 
these elements. We only know this much with certainty, 
as I have already (p. 190) had occasion to remark, that 
a part of the original corpuscular elements of the blood 
proceed just as directly from the embryonic formative 
cells of the ovum, as all the other tissues which build 
themselves up out of them. We know, moreover, 
that in the first months of the existence even of the 
human embryo, divisions take place in the cells, 
whereby an increase in the number of them present in 
the blood itself is produced. But after this time all is 
obscure, and this obscurity indeed corresponds pretty 


RED BLOOD-CORPUSCLES—THEIR ORIGIN. 259 


exactly with the period at which the corpuscles in the 
blood of man and the mammalia cease to exhibit nuclei. 
We can only say that we are acquainted with no fact 
whatever which speaks in favour of a further independ- 
ent development, or of a cell-division, in the blood, but 
that everything points to the probability of a supply 
from without. The only hypothesis which has in more’ 
recent times been advanced with regard to the independ- 
ent development of the blood-corpuscles in the blood 
itself, is that of G. Zimmermann,* who assumed that 
there were little vesicles present in the blood, which gra- 
dually grew by intussusception whilst circulating with it, 
and ultimately constituted the real blood-corpuscles. 
Now little corpuscles certainly do occur in the blood (Fig. 
52, h), only, when they are more accurately examined, 
a peculiarity reveals itself which is unknown in young 
embryonic forms, namely that they oppose an extraordi- 
nary degree of resistance to the most different agencies. 
In their ordinary state they are of a beautiful dark red, 
the colour being very intense and frequently nearly 
black ; if they are treated with water or acids which dis- 
solve the ordinary red corpuscles with ease, it is observed 
that the little bodies require a very much longer time 
before they disappear. Upon adding a large quantity of 
water to a drop of blood, they will be seen to remain for 
a considerable time after the other corpuscles have dis- 
appeared. This peculiarity accords best with what occurs 
in the changes which take place in the blood, when it is 


* Zimmermann has recently (‘ Archiv f. path. Anat. und Phys.,’ vol. xviii., pp. 
221-242) given us a more explicit statement of his views, and from it we gather 
that he considers the blood-corpuscles to originate in small, colourless vesicles 
which are introduced from the chyle into the blood and may be seen in it when its 
fluidity has been preserved by means of salts, But probably these vesicles are only 
artificial products, similar to those described nearly ten years ago by Harting 
(‘ Nederl. Lancet,’ 1851, 3d ser., Ist Jaarg., p. 224).—From a MS. Note by the 
Author. 


260 LECTURE XI. 


extravasated or remains for a long time stagnant within 


the vessels. Such changes undoubtedly lead to a de~ ; “ae 


struction of the corpuscles, so that in the case of the cir- 
culating blood also the conclusion may with great proba- 
bility be drawn, that the bodies in question are not young 
forms, engaged in development, but on the contrary old 
ones in process of decay. I agree therefore essen- 
tially with Karl Heinrich Schultz’s view, who has de- 
scribed these bodies under the name of melanic (mela- 
nése) blood-corpuscles, and regards them as the precur- 
sors of the moulting of the blood (Blutmauserung)—pre- 
paring for the really excrementitious transformations. 

There are certain conditions in which the number of 
these corpuscles becomes extremely large. In very 
healthy individuals very few of them are found, only in 
the blood of the vena porte Schultz believes he has 
always observed a considerable number. It is certain, 
however, that there are diseased conditions in which their 
number becomes so large, that a greater or smaller quan- 
tity of them is met with in nearly every drop of blood. 
These conditions cannot however as yet be classed in de- 
finite categories, because but little attention has been 
excited with regard to them. They are found in slight 
forms of intermittent fever, in cyanosis after cardiac dis- 
ease, In typhoid-fever patients, in the fever accompany- 
ing ichorous infection after operations, and in the course 
of epidemic disorders, still always in such diseases as are 
accompanied by a rapid exhaustion of the mass of blood 
and give rise to cachectic and anzemic states. This is one 
of the processes in which clinical observation also might 
lead to the conclusion that an abundant destruction was 
going on in the constituents of the blood within the ves- 
sels. | 

In addition to these changes we have precise know- 
ledge concerning another class distinguished by quantita- 


CHLOROSIS. : 261 


‘ tive changes in the number of the corpuscles, These 


* . _ ¢onditions, of which Chlorosis is the principal represéeh- 


' tative, offer a certain resemblance to those which are 
‘accompanied by an increase in the number of the colour- 
less blood-corpuscles, to leukeemia in a narrower sense 
of the word and the merely leucocytotic states. Chlo- 
rosis is distinguished from leuksemia by the circumstance 
that the entire number of the corpuscles is smaller. 
Whilst in leukzemia colourless corpuscles in some sort 
take the place of the red ones and a real diminution in 
the number of the cellular elements in the blood is not 
produced, in chlorosis the elements of both kinds become 
less numerous, without the occurrence of any definite 
disturbance in the numerical relation existing between 
the coloured and colourless corpuscles. This points to a 
generally diminished formation, and, if we may conclude 
(as I certainly think one can at the present moment 
scarcely help doing), that the red corpuscles also. are 
brought to the blood from the spleen and. lymphatic 
glands, all this would indicate that in. chlorosis a dimin- 
ished formation takes place in the blood-glands. Leuke- 
mia is of course much more easily explained, inasmuch 
as in it we find representatives of the whole mass of cel- 
lular elements and can imagine that a part of them, 
instead of being transformed into red corpuscles, are 
pursuing their development as colourless ones. In the 
history of chlorosis, on the contrary, much obscurity still 
prevails, since we cannot positively demonstrate the ex- 
istence of a primary affection of the blood-glands. Ana- 
tomical observations indicate that the foundations of the 
chlorotic ailment are very early laid ; for the aorta and 
the larger arteries are usually, and the heart and sexual 
organs frequently, found imperfectly developed, facts 
which lead us to infer that the disposition is either cun- 
genital or formed in early youth, 


962 | LECTURE XI. 


A third series of conditions may here too be men- 
tioned, which, however, do not affect the form of the 
blood-corpuscles, that, namely, in which the internal con- 
stitution of these elements has undergone changes, with- 
out the production of any definite morphological effect. 
Here we have essentially to deal with functional disturb- 
ances which are probably connected with more subtle 
changes in the composition of the blood, changes in the 
proper respiratory substance (respiratorische Substanz). 
For just as in muscles we find the substance of the pri- 
mitive fasciculus, the compact mass of syntonine, to be 
the contractile substance, so in the contents of the red 
corpuscles do we recognize the presence of the really 
active, respiratory substance. This under certain cir- 
cumstances undergoes changes which render it incapable 
of continuing its functions, a kind of paralysis, if you 
will. That something of the kind has occurred we see 
from the fact that the corpuscles are no longer capable 
of absorbing oxygen, as may be directly proved by expe- 
riment. That molecular changes in the composition of 
the blood are here really at work, we find satisfactory 
evidence in the action of poisonous substances which, 
even in extremely minute quantity, so change the hema- 
tine that it is thrown into a kind of paralysis. To these 
substances belong a part of the volatile compounds of 
hydrogen, for example, arseniuretted and cyanuretted 
hydrogen, and further, according to Hoppe’s investiga- 
tions, carbonic oxide, of all of which comparatively very 
small quantities are sufficient to diminish the respiratory 
power of the corpuscles. Analogous conditions have 
already long since been observed by many in the course 
of typhoid fevers, in which the capability of taking up 
oxygen decreases in proportion as the disease assumes a 
severe and acute character. Microscopically, however, 
with the exception of a few melanic corpuscles, scarcely 


THE NERVOUS SYSTEM. ? 263 
anything is to be seen; chemical experiment and the 
coarse perception of the naked eye in this instance alone 
discover the occurrence of peculiar changes. It may 
therefore be said that in this quarter really the most has 
yet to be done. We have rather presumptive evidence 
than facts. 

If now we briefly sum up what I have laid before you 
concerning the blood, we see, either that certain sub- 
stances find their way into it, which exercise an injurious 
influence upon its cellular elements and render them in- 
capable of performing their functions; or that from a 
definite point, either from sources external to the body, 
or from some organ, matters are conveyed into it, which 
thence exercise an injurious influence upon other organs ; 
or finally that its constituents are not replaced and rege- 
nerated in a regular manner. Nowhere in this whole 
series do we find any one condition, indicating that defi- 
nite changes once set on foot in the blood itself can be 
permanently maintained, in other words that a perma- 
nent dyscrasia is possible, unless new agencies derived 
from a definite source are continually brought to bear 
upon the blood. This is the reason why I began by call- 
ing your attention to this point of view, which I conceive 
to be of extreme importance in practice also, namely, 
that in all forms of dyscrasiz the chief point is to search 
for their local origin. 


Let us now proceed to the consideration of another 
subject which comes next in historical importance, namely 
the structure and arrangement of the nervous system. 

The great mass of the nervous system consists of 
fibrous constituents. It is to them that nearly all the 
finer physiological discoveries, which the last fifteen 
years have brought with them, have reference, whilst 
the remaining portion of the nervous system, in quantity 


264 LECTURE XI. 


much smaller, namely, the grey, or ganglionic, substance, 
has hitherto opposed difficulties even to histological in- 
vestigation which are still far from being overcome, so 
that the experimental examination of this substance has 
scarcely been able to be taken in hand. It is indeed 
often maintained that a great deal is now known about 
the nervous system, but our knowledge is for the most 
part confined to the white substance, the fibrous portion, 
whilst we are unfortunately obliged to confess that, both 
in an anatomical, but more especially in a physiological 
point of view, we are still involved in the greatest uncer- 
tainties with regard to the grey substance, which, as far 
as its functions are concerned, manifestly holds a much 
higher position. 

As soon as we consider the question of the influence 
exercised by the nervous system in the different pro- 
cesses of life, anatomically, a single glance suffices to show, 
that the point of view which: neuro-pathologists have 
been accustomed to set out with, is a very erroneous one. 
For they fancied they saw in the nervous system an un- 
usually simple whole, from the unity of which resulted 
the unity of the body in general, of the whole organism. 
But even though one has nothing but very rough anato- 
mical ideas concerning the nerves, still one ought not to 
shut one’s eyes to the fact that this unity is in a very 
sorry plight, and that even the scalpel demonstrates the 
nervous system to be an apparatus composed of an ex- 
tremely large number of parts of relatively equal value 
without any single discoverable central point. The more 
accurately we make our histological investigations, the 
more do the elements multiply, and the ultimate compo- 
sition of the nervous system proves to be disposed upon 
a plan analogous to that which has been followed in all 
the other parts of the body. An infinite quantity of 
cellular elements manifest themselves side by side, more 


THE NERVOUS SYSTEM—PERINEURIUM. 265 


or less autonomous, and in a great measure independent 
_of one another. 

If in the first instance we exclude the ganglionic sub- 
stance and confine ourselves simply to the fibrous matter, 
we have on the one hand the real (peripheral) nerves in 
the narrower sense of the word, and on the other the 
large accumulations of white medullary substance, of which 
the greater part of the cerebrum, cerebellum, and the 
columns of the spinal marrow is composed. The fibres 
of these different parts are indeed on the whole similarly 
constructed, but disclose in their intimate structure such 
numerous, and in part, such considerable differences, that 
there are spots, with regard to which even at this very 
moment we cannot say with certainty whether the ele- 
ments we have before us are really nerves, or belong to 
an altogether different kind of fibres. The greatest cer- 
tainty has been acquired with regard to the structure of 
the ordinary peripheral nerves ; in them the following 
can generally be distinguished with tolerable facility. 

All the nerves which can be followed with the naked 
eye contain a certain number of subdivisions, or fasci- 
euli, which afterwards separate in the form of branches 
or twigs. On-tracing out these individual twigs which 
keep continually dividing, we find that the nerve under 
nearly all circumstances retains a fascicular arrangement 
until nearly its ultimate divisions, so that every fascicu- 
lus in its turn comprises a greater or less number of so- 
called primitive fibres. The term, primitive fibre, which 
is here employed, was originally selected, because a 
nerve-fasciculus was regarded as analogous to the primi- 
tive fasciculus of a muscle. This notion afterwards be- 
came almost obsolete, and Robin was the first who in 
more recent times again directed attention to the sub- 
stance which holds the fasciculus together and which he 
called perineurium. It consists of very dense connective 


266 LECTURE XI. 


tissue, which upon the addition of acetic acid, it seen to 
contain small nuclei, and is different from the looser con- 
nective tissue which in its 
turn holds the fasciculi to- 
gether and constitutes the so- 
called neurilemma. 

When we use the term 
nerve-fibre alone in its histo- 
logical sense, we always mean 
the primitive fibres, and not 
the fasciculi which to the 
naked eye look like fibres. 
These ultimate fibres in their turn possess, one and all, 
a special external membrane, which, when it has been 
entirely freed from its contents—a matter certainly very 
difficult to accomplish, but sometimes occurring sponta- 
neously in pathological conditions, as for example in cer- 
tain states of atrophy—displays nuclei upon its walls 
(Fig. 5, c). Within these membranous tubes lie the pro- 
per nerve-contents, which in ordinary nerves may again 
be divided into constituents of two descriptions. These 
can scarcely be distinguished apart in a nerve which is 
quite fresh ; but in a short time after it has perished or 
been cut out, or after the action of any medium upon it, 
they at once separate very distinctly from one another, 
one of the constituents undergoing a rapid change which 
has generally been termed coagulation, and by means of 
which it is marked off from the other constituent (Fig. 
78). When this has taken place there is distinctly seen 
in the interior of the nerve-fibre, the so-called axis-cylin- 


inte a We 





> 

Fig. 77. Transverse section through one of the trunks of the brachial plexus, 
1, 7. Neurilemma, from which one thicker partition 7’ and finer prolongations, indi- 
cated by light-coloured lines, run through the nerve and divide it into small fasci- 
culi. These exhibit the dark, punctated, transverse sections of the primitive fibres, 
and between them is seen the perineurium. 80 diameters. 


NERVE-FIBRES—AXIS-CYLINDER—MEDULLARY SHEATH. 267 


der (the primitive band of Remak), a very fine, delicate, 
pale structure ; and round about it a tolerably firm, 
dark mass, here and there run- 
ning together, the nerve-me- 
dulla or medullary sheath {white 
substance of Schwann] ; this 
fills up the space between the 
axis-cylinder and the external 
membrane. But the nerve- 
tube is generally so tightly 
filled with its contents that, 
when viewed in the ordinary 
way, scarcely anything is seen 
of the separate constituents, 
the axis cylinder being always 
with difficulty visible within the 
medullary substance. Hence 
the fact may be accounted for, 
that its very:existence was disputed for years and the 
view proclaimed by many, that it was also an appearance 
due to coagulation, produced by a separation of the ori- 
ginally homogeneous contents into an internal and exter- 
nal mass. This view is however unquestionably incor- 
rect: every mode of examination at last discloses this 
primitive band ; even in transverse sections of nerves the 
axis-cylinder is very distinctly seen in the interior, with 
the medulla round about it. 

It is the so-called nerve-medulla which gives the nerve- 
fibres in general their white appearance ; wherever the 
nerves contain this constituent, they look white ; 


Fig. 78. 





Fig. 78. Grey and white nerve-fibres. A. A grey, gelatinous nerve-fasciculus 
from the root of the mesentery, after the addition of acetic acid. 2B. A broad white 
primitive fibre from the crural nerve: a the axis-cylinder laid bare, 7, » a varicose 
state of the fibre with its medullary sheath ; at the end at m, m the medullary mat- 
ter(myeline) protruding in convoluted forms. (@. A fine, white primitive fibre 
from the brain, with its axis-cylinder protruding. 300 diameters. 


268 LECTURE XL 


wherever it is wanting, they appear translucent and grey. 
There are therefore nerves which are akin in colour to 
ganglionic matter, are comparatively transparent and 
possess a more clear and gelatinous appearance than the 
others ; and they have thence been called grey or gela- 
tinous nerves (Fig. 78, A). Between the grey and white 
nerve-substance therefore there does not exist the differ- 
ence that the one is ganglionic and the other fibrous, 
but only this, that the one contains medulla and the other 
does not. In general the absence of medulla in a nerve 
stamps it as one of a lower and more imperfect kind, 
whilst the presence of this substance announces a more 
abundant nutrition and a higher development in the 
part. 

Not long ago I made an observation in which a direct 
illustration of the ee importance of these two con- 
ditions was displayed in a 
very unexpected manner, the 
usually translucent grey nerve 
substance having been trans- 
formed into an opaque and 
white matter, namely in the 
retina. I found namely entire- 
ly by accident one day, in the 
eyes of aman in whom I was 
looking for changes of quite 
another kind—round about 
the papillaof the optic nerve, where the uniformly trans- 
lucent retina is ordinarily seen—a number of whitish, 


Fie. 79. 








Fig. 79. Medullary hypertrophy of the optic nerve within the eye (Cf. ‘ Archiv f. 
pathologische Anatomie und Physiologie,’ vol. x., p. 190). .A. The posterior half 
of the globe of the eye, seen from before ; from the papilla of the optic nerve pro- 
ceed in four directions radiating strie of white fibres. B. Fibres from this optic 
nerve in the retina, magnified $00 times: a, a pale, ordinary, slightly varicose fibre, 
6, one with a gradually thickening medullary sheath, c, a similar one with its axis- 
cylinder protruding. 


MEDULLATED AND NON-MEDULLATED NERVES. 969 


radiating strie like those which one sometimes meets 
with upon a small scale in dogs, and pretty constantly in 
rabbits in different directions. The microscopical exa- 
mination showed that, like as in these animals, medullated 
fibres had developed themselves in the retina, and that 
its fibrous layer had become thicker and opaque in con- 
sequence of the assumption of medullary substance. On 
examining the individual fibres I found, on tracing them 
from the fore and middle parts of the retina backwards 
towards the papilla, that they gradually increased in 
breadth, and at the same time displayed, at first in an 
almost imperceptible, but afterwards in a very striking 
manner, an investing layer of medulla. This is a kind 
of transformation, therefore, which essentially impairs 
the functions of the retina, for this delicate membrane 
becomes thereby more and more impervious to light, in- 
asmuch as the white substance does not suffer the rays 
of light to pass through. 

The same change occurs in nerves during their deve- 
lopment. A young nerve is a delicate, tubular structure, 
provided with nuclei at certain intervals and containing 
a pale grey substance. The medulla does not appear 
until afterwards, and then the nerve becomes broader 
and the axis-cylinder becomes distinctly defined. Itmay 
be said therefore that the medullary sheath is not an 
absolutely necessary constituent of a nerve, but is added 
to it only when it has arrived at a certain stage in its 
development. 

Hence it follows that this substance, which was for- 
merly regarded as the essential constituent of a nerve, 
according to present views plays a subordinate part. 
Those only who do not even now admit the existence of 
the axis-cylmder, regard the white substance of course 
not only as the greatly predominating constituent, but 
also as the really active element of the nerve-contents. 


970 | LECTURE XI. 


Now it is very remarkable that this same substance is one 
which most extensively prevails in the animal body. I 
had, curiously enough, in the first instance in the exami- 
nation of lungs come across forms which presented very 
similar qualities to those which we observe in the me- 
dulla of the nerves. Although this was very surprising, 
yet I did not really think there was an actual correspond- 
ence, until I was gradually led by a series of further ob- 
servations which accumulated in the course of several 
years, to examine a number of tissues chemically. The 
result showed, that there scarcely exists a tissue rich in 
cells in which this substance does not occur in large 
quantity ; still it is only in the nerve-fibre that we ob- 
serve the peculiarity, that the 
substance separates as such, whilst 

B in all other cellular parts it is 
( 0 @ @ contained in a finely divided state 
yo pe in the interior of the cells, and is 
f a only set free when the contents 
undergo a chemical change, or are subjected to the action 
of chemical reagents. From blood-cells, from pus-cor- 
puscles, from the epithelial cells of the most various glan- 
dular parts, from the interior of the spleen and similar 
glands unprovided with excretory ducts, this substance 
can in every case be obtained by extraction. It is the 
same substance which forms the principal constituent of 
the yellow mass of yolk in the hen’s egg, whence its taste 
and peculiarities, especially its peculiar tenacity and vis- 
cidity which are employed for the higher technical pur- 
poses of the kitchen, are familiar to every one. It is this 
substance, for which I have proposed the name of medul- 


Fig. 80. 





Fig. 80. Drops of medullary matter (myeline—according to Gobley, lecithine). 
A, Differently shaped drops from the medullary sheath of cerebral nerves, after they 
have become swollen up with water. B. Drops from decomposing epithelium from 
the gall-bladder in their natural fluid. 800 diameters. 


AXIS-CYLINDER (ELECTRICAL SUBSTANCE). vel 


lary matter (Markstoff), or myeline, that in extremely 
large quantity fills up the interval between the axis- 
cylinder and the sheath in primitive nerve-fibres. 

* Tf the nutrition of a nerve suffer disturbance, this sub- 
stance diminishes in quantity and indeed may under cer- 
tain circumstances totally disappear, so that a white 
nerve may be again reduced to the condition of a grey 
or gelatinous one. This constitutes grey atrophy, or 
gelatinous degeneration, in which the nerve-fibre in itself 
continues to exist, and only the peculiar accumulation 
of medullary matter has been affected. Herein you may 
seek for an explanation of the circumstance, that in many 
cases where, in accordance with the results of anatomical 
investigation, it was formerly thought one might expect 
to find a part completely incapable of fulfilling its func- 
tions, proof has been afforded by means of clinical obser- 
vation, aided by electricity, that the nerve is still capa- 
ble of performing its functions, although in a less degree 
than normal. Hence too it is manifest that the medulla 
cannot be the constituent in which lie vested the func- 
tions of the nerve as such. To the same conclusion phy- 
sical investigations also have generally led, and at the 
present time therefore the axis-cylinder is pretty gene- 
rally looked upon as the really essential constituent of 
the nerve, which is also present in pale nerves, whilst in 
white ones it can only be distinctly isolated by the sepa- 
ration of the investing medullary sheath. The axis-cylin- 
der would therefore seem to be the real electrical sub- 
stance of natural philosophers, and we may certainly 
admit the hypothesis which has been advanced, that the 
medullary sheath rather serves as an isolating mass, which 
confines the electricity within the nerve itself, and allows 
its discharge to take place only at the non-medullated 
extremities of the fibres. | 

The peculiar nature of the medullary matter most fre 


272 LECTURE XI. 


quently displays itself in this way, that when a nerve is 
torn across or cut (Fig. 78, m, m), the medulla usually 
protrudes from it, presenting, especially after it has been 
acted upon by water, a peculiar striated appearance (Fig. 
80, A). It takes up water namely, which is a proof that 
it is not a neutral fatty substance in the ordinary sense 
of the term, but can at most, on account of its great 
power of swelling up, be compared to certain saponace- 
ous compounds. The longer the action of the water lasts, 
the longer are the masses which protrude from the nerve. 
They have a peculiar, ribbon-like appearafice, keep con- 
tinually acquiring new streaks and layers, and give rise 
to the most singular shapes. Frequently also fragments 
become detached and swim about, forming peculiar, stra- 
tified bodies, which in recent times have been confounded 
with corpora amylacea, but are distinguished 
from them in the most positive manner by their 
chemical reactions. 

With regard to the histological varieties of 
nerves amongst themselves, investigation shows 
that in different parts more or less highly deve- 
loped forms greatly predominate. On the one 
hand, namely, the nerves are essentially distin- 
guished by the breadth of their primitive fibres, 
on the other hand, by the presence of medulla. 
We have very broad, middle-sized and small 
white fibres, and in like manner broad and fine 
grey fibres. A very considerable size is generally speaking 
but seldom attained by the grey ones, because the size 
of a nerve depends more upon the greater or less quan- 
tity of medulla it contains than upon the volume of the 
axis-cylinder, but still variations present themselves 








Fig. 81. Broad and narrow nerve-fibres from the crural nerve with the medullary 
substance irregularly swollen up. 300 diameters. 


> 


VARIETIES OF NERVE FIBRES. 273 


everywhere, so that some nerves are coarser and others 
finer. 3 
Generally, we may say, that the primitive fibres usu- 
ally become finer in the terminal portions of nerves, and 
that the ultimate ramifications of these latter are wont to 
contain comparatively the finest fibres ; still this is not 
an absolute rule. In the optic nerve we commonly find 
from the very moment of its entrance into the eye only 
very narrow, pale fibres (Fig. 79, a), whilst the tactile 
nerves of the skin present quite up to their terminations 
comparatively: broad and dark bordered fibres (Fig. 83). 
It has not yet been found possible to arrive at any cer- 
tain opinion with regard to the import of the different 
_ kinds of fibres from their breadth and the proportion of 
medulla they contain. For.a time it was believed that 
a distinction of this sort could be established between 
them, namely, that the broad fibres were to be regarded 
as derived from the real cerebro-spinal parts, the fine 
ones as parts of the sympathetic ; but this is not found 
to be borne out by facts, and all that can be said is, that 
the ordinary peripheral nerves certainly are abundantly 
provided with broad fibres, whilst the sympathetic nerves 
contain a comparatively larger portion of fine ones. In 
many places, as for.example in the abdomen, grey, broad 
fibres predominate (Fig. 78, A), with regard to the ner- 
vous nature of which doubts are still entertained by 
some. For the present, therefore, no definite conclu- 
sions can be drawn as to any difference in the functions 
of a nerve from its mere structure, although it can 
scarcely be doubted that such differences must exist, and 
that a broad fibre must exhibit other properties, even if 
only quantitatively different, than a fine one, a medul-. 
lated fibre others than a non-medullated one. However 
concerning all this nothing is at present known with cer- 


tainty ; and since it has been demonstrated by more 
18 


974 LECTURE XI. 


delicate physical investigations that the nerves, which 
had been previously assumed only to conduct in the one 
or the other direction, possess the power of conduction 
in both directions, I should not, I think, be justified in 
here advancing any hypotheses with regard to their cen- 
tripetal or centrifugal conduction. 

The great difference, gentlemen, which is to be re- 
marked in regard to the functions of individual nerves, 
cannot as yet be referred so much to any difference of 
structure in them, as to the peculiarity of the structures 
with which the nerve is connected. Thus on the one 
hand the special function of the central organ from 
which the nerve proceeds, and on the other, the special 
nature of its distal termination, afford a clue to its own | 
specific functions. 

With reference to the terminations which the nerves 
present at their peripheral extremities, histology has, I 
should say, in the course of the last few years celebrated 
its most brilliant triumphs. Previously it was, as you 
well know, a matter of dispute whether the nerves ended 
in loops or in plexuses, or whether their terminations 
were free, and the one or the other opinion was held 
with equal exclusiveness. Now, we have examples of 
most of these modes of termination, but the fewest of 
that form which was for a time regarded as the regular 
one, namely the termination in loops. 

The most manifest form of termination, though the 
one whose functions are, singularly enough, even now the 
least known, is that in the so-called Paciman or Vatertan* 
bodves—organs, concerning the import of which we are 
still unable to make any statement. They are found in 
man comparatively most marked in the adipose tissue 
of the ends of the fingers, but also in tolerably large 


* Vater was professor at Wittenberg, and died in 1751. 


PACINIAN BODIES. O75 


numbers at the root of the mesentery ; most distinctly 
and readily, however, in the mesentery of the cat, in 
which they extend a considerable distance up, whilst in 
the human body they are situated only at the root of the 
mesentery, where the duodenum comes in contact with 
the pancreas in the neighborhood of 
the solar plexus. Moreover they pre- 
sent great variations in different indi- 
viduals. Some have very few, others 
a great number, of them, and itis very 
possible that certain individual pecu- 
liarities result therefrom. Thus I 
have, for example, on several occasions 
found a great number of these bodies 
in lunatics, though I do not wish at 
present to lay any great stress upon 
this discovery. 

A Pacinian body, as seen with the 
naked eye, is of a whitish colour, usu- 
ally oval and somewhat pointed at one 
end, from a line to a line and a half 
(1—13’”) long, and firmly attached to 
a nerve in such a way that a single 
primitive fibre passes into each body. 
It presents a comparatively large num- 
ber of elliptical and concentrical layers, 
which at the upper end are in. pretty close contact, but 
at the other are separated by a wider interval, and en- 
close in their interior an oblong space generally some- 


Fig. 82. 


= 


WY 
l 
vi 
N\ Y / 
i 
Ni\\ 
SQ 


SSS 
Ze 





Fig. 82. Vaterian or Pacinian body from the subcutaneous adipose tissue of the 
end ofa finger, 8. The peduncle, consisting of a dark-bordered, medullated pri- 
mitive nerve-fibre n, and the thick perineurium p, p provided with longitudinal 
nuclei. C. The body itself with the concentric layers of the perineurium which is 
swollen out into a bulbous shape—and the central cavity, within which the pale 
axis-cylinder is seen running along and terminating in a free extremity. 150 
diameters, 


276 LECTURE XI. 


what more pointed towards the upper end. Within 
these layers nuclei can be distinctly seen disposed in 
regular order, and on following the layers towards the 
stem of the nerve, they are there ‘observed finally to pass 
into the perineurium which is in this part very thick. 
They may therefore be regarded as gigantic developments 
of the perineurium, which however only enclose a single 
nerve-fibre. Now on tracing the nerve-fibre itself we 
observe that its medullated portion usually extends only 
up to the beginning of the body, when the medulla dis- 
appears and the axis-cylinder is seen continuing its 
course alone. Itthen runs on through the central cavity, 
and terminates at no great distance from the upper end 
generally simply, yet often in a little bulbous swelling* 
and in the mesentery very frequently in a spiral coil. 
In rare cases it happens that the nerve divides and seve- 
ral branches pass into the body. But in every case we 
seem to have before us a mode of termination. What 
these bodies signify, what office they perform, whether 
they have anything to do with the function of sensation, 
or whether their province is to develop any one of the 
properties of the nervous centres, we are as yet entirely 
ignorant. 

A certain degree of resemblance to these structures is 
exhibited by the tactile bodies which have been recently 
so much the subject of discussion. When the skin and 
more especially the sensitive part of it 1s microscopically 
examined, two sorts of papille, as was first discovered by 
Meissner and Rud. Wagner, are distinguished, the one 
narrower, the other broader, though certainly interme- 
diate forms are met with (Fig. 83). In the narrow ones 
we constantly find a simple, in broader ones of the same 
class a branching, vascular loop, but no nerve. This 


* Quite recently Jacubowitsch has, as he thinks, discovered a ganglion cell in 
this part.—/S. Note of Author. ; 


TACTILE BODIES. QtT 


point is so far of importance, that we have, by means of 
these observations, been made acquainted with a new 
nerveless structure. In the other kind of papillee we very 
frequently find no vessels at all, but on the other hand 
nerves, and those peculiar structures which have been 
designated tactile bodies. 

A tactile body manifests itself as an oblong-oval struc- 
ture, tolerably distinctly marked off from the remainder 
of the papilla, and has, with some degree of boldness in- 
deed, been compared by Wagner to a fir-cone. It is 
generally rounded off at the upper and lower end, and 
does not exhibit a longitudinal striation, as the Pacinian 
bodies do, but on the contrary transverse nuclei. Now a 
nerve runs up to every one of these bodies, and from 
every one of them a nerve returns, or more correctly, 
we usually see two nervous filaments, generally pretty. 


Fig. 83. 


i 
h 


hp 


y 

) 
i 
WV 
Hy 





Fig. 83. Nervous and vascular papill from the skin of the end of a finger, after 
the separation of the epidermis and rete Malpighii. .A. Nervous papilla with a tac- 
tile body, up to which ascend two primitive nerve-fibres n; at the base of the pa- 
pilla fine elastic networks e, from which fine fibres radiate, between and on which 
connective-tissue-corpuscles are to be seen. B, CO, D. Vascular papillw, with, at C, 
simple, at B and D, branching vascular loops, and in addition fine elastic fibres and 
connective-tissue-corpuscles ; p. the papillary body running its horizontal course, at 
¢ fine stellate cells belonging to the cutis proper. 300 diameters, 


278 LECTURE XI. 


close to one another, which can be readily traced up to 
the side or base of the body. After this point their 
course is very doubtful, and in different cases the condi- 
tions vary so much that we have not yet succeeded in 
making out with certainty the relation of the nerves to 
these bodies. In many cases, namely, the nerve is very 
distinctly seen to ascend and also to entwine itself 
around the body. Sometimes it seems as if the body 
really lay in a nervous loop, and thus the possibility of a 
more concentrated action on the part of external agen- 
cies upon the surface of the nerve was provided for. At 
other times again it looks as if the nerve came to a ter- 
mination much sooner, and buried itself in the body. 
Some have assumed, with Meissner, that the body itself 
belongs to the nerve which resolves itself into it. This 
I do not hold to be correct, and the only point which 
seems to me to be doubtful is, whether the nerve ends 
in the body or forms a loop around it. 

Apart from anatomical and physiological considera- 
tions, this example is of great value in the interpreta- 
tion of pathological phenomena, because we here find 
two complete contrasts in parts which in themselves are 
quite analogous ; for, on the one hand, we have nerve- 
less but vascular, on the other, non-vascular, papillae, 
yet provided with nerves. The peculiar relations which 
the layers of the rete mucosum and epidermis bear to 
the two kinds of papille, do not appear to present 
any essential differences. They are nourished just as 
perfectly over-the one sort as over the other, and seem 
to be just as little provided with nerves over the one as 
over the other. 

These are facts which indicate a certain independence 
in individual parts and furnish distinct evidence that 
parts of considerable size and even richly provided with 
nerves can subsist, maintain their existence and perform 


TACTILE BODIES. 279 


their functions without vessels, and that on the other 
hand parts which relatively contain numerous vessels, can 
absolutely dispense with nerves without incurring any 
disturbance in the state of their nutrition. 


diye viet @ ad eee WAS ict see GE De 


MARCH 31, 1858. 


THE NERVOUS SYSTEM. 


Peripheral terminations of the nerves—Nerves of special sense—The skin and the 
distinction of vessel-, nerve-, and cell-territories in it—Olfactory mucous mem- 
brane—Retina—Division of nerve-fibres—The electrical organ of fishes—Mus- 
cles—Further consideration of nerve-territories—Norvous plexuses with gan- 
glioniform enlargements—Intestines—Errors of the neuro-pathologists. 

The great nervous centres—Grey substance—Ganglion- [nerve-] cells containing 
pigment—Varieties of ganglion-cells ; sympathetic cells in the spinal marrow 
and brain, motor and sensitive cells, Multipolar (polyclonous) ganglion-cells— 
Different nature of the processes of ganglion-cells. 


I return, gentlemen, to-day once more to the skin. 
The difference which exists between the individual pa- 
pille of the skin seems to me so important theoretically, 
that I think I must claim your special attention to it. In 
the greater number of the papillae we see, as I mentioned 
to you the last time, a single or, when the papilla is very 
large, a branched, vascular loop. The majority of these 
vascular papille have no nerves; others again which 
contain tactile bodies, no vessels. If we imagine the 
vessels and tactile bodies removed, there remains only a 
very small quantity of substance in the papilla, but within 
it there still are morphological elements, and it is easy 
to convince oneself that connective tissue with its corpus- 


cles (which latter after injection are very easily distin- 
280 


* 


NERVES OF SPECIAL SENSE. 281 


guished from the vessels), is in immediate contact with the 
cells of the rete mucosum (Fig. 83). The case is espe- 
cially favourable when, in consequence of any disease, as 
for example small-pox, a slight tumefaction of the whole 
thickness of the skin in the parts affected has taken place, 
and the corpuscles are a little larger than they normally 
are. In ordinary papille it is somewhat more difficult 
to discover these elements, still upon closer examination 
they may be seen everywhere, even by the side of the 
tactile bodies. 

Thus, even in the finest of ‘these prolongations of the 
cutis, it is not an amorphous mass which is found, bear- 
ing a constant relation to the vessels and nerves ; on the 
contrary this mass of connective tissue always manifests 
itself as the one thing invariably present in the structure, 
as the real fundamental constituent of the different (vas- 
cular and nervous) papille, and the individual papille do 
not acquire a different character until in the one case 
vessel, in the other nerves, are added to this funda- 
mental substance. 

We certainly know little concerning the special rela- 
tions which the vascular papille bear to the functions of 
the skin, still it can scarcely be doubted that an import- 
ant relation must exist, and that as soon as we are better 
able to separate the different offices of the skin, greater 
importance will be attached to the vascular papillee also. 
This much however we can even now say, that it is incor- 
rect to imagine that a special nervous branch exists in 
every anatomical division of the skin: just as physiolo- 
gical experiments* show that considerable sensitive dis- 
tricts exist in the skin, so also more minute histological in- 
vestigation teaches us that there is a relatively scanty ter- 
mination of nerves upon the surface. If therefore we 
think fit to divide the skin into definite territories, those 


* The allusion is to Weber's experiments with compasses.—77ans. 


282 | LECTURE XIL 


appertaining to the nerves will, as a matter of course, be 
larger than those belonging to the vessels. But every 
vessel territory (papilla) also which is marked out by a 
single capillary loop is divided into a series of smaller 
(cell-) territories, all of which certainly lie along the 
banks of the same vessel, but still have an independent 
existence, each of them being provided with a special cel- 
lular element. 

In this manner it is very easy to explain how within a 
papilla a single (cell-) territory may become diseased. 
Suppose, for example, that such a territory swells up, in- 
creases in size, and continually keeps shooting farther 
and farther upwards, then arborescent ramifications may 


Fig. 84. 





arise (accuminate [spitzes] condyloma*) without the 
whole papilla’s being affected in a like manner. The 


Fig. 84. The fundamental substance (connective tissue) of an acuminate condy- 
loma of the penis with freely budding and branching papille, after the epidermis 
and the rete mucosum have been completely detached. 12 diameters. 


* The Germans speak of condylomata Jata and acuminata. The condyloma latum 
is ¢nvariably of syphilitic origin, and is identical with the plaque muqueuse of the 
French, who never use the term condylome in this sense. Condyloma acuminatum, on 
the contrary (by the French termed simply condylome), is not syphilitic in its nature, 
but frequently occurs in gonorrhea, though it is also met with independently of this 
disease.— From a MS. Note by the Author. 


VESSEL-, NERVE-, AND CELL-TERRITORIES. — 288 


vessel does not shoot up until later and forces its way 
into the branches when they have already attained a cer- 
tain size. It is not the vessel which pushes out the parts 
by its development, but the first signs of development 
always show themselves in the connective tissue of the 
papilla. The study of the conditions of the skin therefore 
affords special interest to those who wish to devote them- 
selves to the critical examination of the doctrines held 
concerning general pathology. And first with regard to 
the neuro-pathological views, it is quite inconceivable 
how a nerve which lies in the middle of a whole group 
of nerveless parts, can contrive to force a single papilla 
from among this group, with which it has not the slightest 
connection, into a state of pathological activity in which 
the remaining papille of the same nerve-territory take 
no share. Just as difficult is it, in the diseases of non- 
vascular papillae, to find an explanation which shall 
accord with the views of a humoro-pathologist. Hven 
when ina vascular papilla the different cell-territories 
attain different states, these would not admit of a ready 
explanation, if we were to regard the whole process of 
nutrition in a papilla as directly dependent upon the 
general condition of the vessel which supplies it. 

Similar considerations might be entered upon with 
regard to all points of the body. Still we have in the 
skin a particularly favourable example for demonstrating 
how very incorrect it is to regard all vessels as subject 
to a particular nervous influence. There are a number 
of vessels which are entirely removed from the influence 
of all nerves, and, if we still confine our attention to 
the skin, the influence which a nerve is in a condition to 
exercise, 1s limited to this, that the afferent artery, which 
supplies a whole series of papille in common (Fig. 44) 
may by its means be brought into an altered condition, » 
so that a contraction or dilatation, and in correspondence 


984 LECTURE XII. 


with these states a diminished or increased supply of 
blood to a considerable district, takes place. 

If now we return from this digression to our real sub- 
ject, you will recollect that I had described to you my 
ignorance concerning the real mode of termination which 
the nerves have in the tactile bodies. Whether the 
nerve ultimately forms a loop, or in any manner directly 
terminates in the internal substance of the body, is not, I 
think, as yet absolutely decided. 

If now we consider other instances of the terminations 
of nerves, nowhere does any probability manifest itself 
that they really do form loops. In every case in which 
more certain knowledge has been acquired, the proba- 
bility has on the contrary always become greater, that the 
nerves either terminate in a large plexus or recticular 
expansion ; or that they end in special apparatuses, con- 
cerning which it is still doubtful whether they are pecu- 
liar processes of a particular shape, into which the nerves 
shoot out at their extremities, or whether they consti- 
tute peculiar parts, non-nervous in their nature, to which 
the nerves attach themselves. This latter mode of ter- 
mination is, it would appear, characteristic of most of the 
higher organs of sense, but in no single instance, in con- 
sequence of the extreme difficulty which the investigation 
of these parts presents, have any views been proposed 
which have met with universal assent. Notwithstanding 
the numerous investigations into the structure of the 
retina and cochlea, the mucous membrane of the nose 
and mouth, that have been made in the course of the last 
few years, it must be confessed that the ultimate points 
of histological detail have not as yet been altogether 
satisfactorily settled. In nearly all cases there remain 
two possible ways in which the nerves may terminate. 
According to some their terminations are connected with 
special structures which, according to the language 








RETINA. 285° 


hitherto employed, cannot be regarded as being of a ner- 
vous nature, but are peculiar appendages of the nerves, 
though they are certainly stated by other observers to 
be directly connected with nerve-fibres, as for example 
in the nasal mucous membrane. This namely is regu- 
larly clothed with cylindrical epithelium, which is plen- 
tifully provided with cilia and forms several layers, lying 
one above the other, so that there are several rows of 
cells covering one another. In these, according to seve- 
ral recent observers, cells are met with, which terminate 
in a somewhat long filament, and do not, like other epi- 
thelial cells, end upon the surface, but run in an inward 
direction, so as to become directly continuous with the 
ends of the nerves. According to others, particularly 
Max. Schultze, on the contrary, and this view seems te 
be the more correct one, peculiar filiform ends of nerves 
force their way out between the epithelium. The objects 
of smell would therefore according to both views really 
come directly in contact with the structures forming the 
terminations of the nerves. Similar epithelium-like struc- 
tures have recently been described as occurring also in 
the mucous membrane of the tongue, seated upon pecu- 
liar papille, which appear to possess a pre-eminently 
nervous character. | 

These structures moreover might lay claim to a certain 
resemblance with the ultimate terminations which we find 
in the case of the optic nerve in the retina, and in that 
of the auditory nerve especially in the cochlea—termina- 
tions, which may in the latter case, as far as their exter- 
nal shape is concerned, be compared to long-tailed epi- 
thelial cells, whilst those in the retina constitute struc- 
tures of peculiar delicacy. In the retina namely the 
optic nerve, after its entrance into the interior of the 
globe of the eye, spreads out in such a way, that its fibrous 
elements run along on the anterior side of the retina, that 


286 LECTURE XII. 


side, namely, which is turned towards the vitreous body 
(Fig. 85, f) ; posteriorly, there follows a stratum of vary- 
ing thickness, which belongs to the retina indeed, but in 
no wise proceeds from the direct expansion of the optic 
nerve. In this layer we see, where it borders upon the 
layer of pigment-cells of the choroid coat, and in imme- 
diate contact with these cells, a peculiar stratum which 
has been subjected to a strange destiny, asmuch as it 
was for a considerable time transplanted to the anterior 


Fig. 85. 


AE 
2 Hee a en aoe if i IK’ 












ao 
a il a 


oe 











OD 






ae ate Als 









ith 
OG i i va 
i a Kae ate 


bili igure 












| Hanon A un 
a We yy IN A 


a HO UNAM vali 




















i 














side of the retina—the famous bacillar layer (layer of 
rods—Stiibchenschicht [membrana Jacobi]) (Fig. 85, s). 
This layer, which belongs to the most easily injured 
parts of the eye, and for this reason in many instances 
escaped the notice of earlier observers, consists, when 
viewed in profile, of a very large quantity of closely 


Fig. 85. A. Vertical section through the whole thickness of the retina, after it 
had been hardened in chromic acid. /. Membrana limitans, with the ascending, 
supporting fibres. f. Fibrous layer of the optic nerve. g. Layer of ganglion-cells. 
n. Grey, finely granular layer, with the radiating fibres passing through it. &. In- 
ternal (anterior) granular layer. 7. Intermediate, or intergranular, layer. k’. Ex- 
ternal (posterior) granular layer. s. Layer of rods and cones. 300 diameters. 
B, C (after H. Muller), Isolated radiating fibres. 


RETINA, vis 287 


packed little rods, arranged in a radiated form, and be- 
tween which at certain intervals appear broader, conical 
bodies. When the retina is viewed from behind, 7. ¢., 
from the choroid coat, we see regularly arranged between 
these cones fine points which correspond to the ends of 
the little rods. 

Now that which intervenes between this bacillar layer 
and the proper expansion of the optic nerve, is likewise 
a very complex affair, in which a series of layers follow- 
ing one another in regular succession can be distin- 
guished. Immediately in front of the bacillar layer 
comes a comparatively thick stratum, which appears to 
be nearly entirely made up of coarse granules, the so- 
called external granular layer (Fig. 85, %’). Then comes 
a thinner layer which generally presents a tolerably 
amorphous appearance, the inter-granular layer (Fig. 
85, 2). Then we again have coarsish granules (the inter- 
nal granular layer) ; these bodies in both layers having 
much the appearance of nuclei (Fig. 85, %). Next fol- 
lows a second layer of a more uniform, finely granular or 
finely striated appearance, and of a more greyish hue 
(Fig. 85, 2), and then only the tolerably thick stratum 
of the optic nerve, which in its turn is bounded by a 
membrane, the membrana limitans (Fig. 85, /), which is 
in close apposition to the vitreous body. Within this 
last layer we see, besides the fibres of the optic nerve, 
and situated behind them, a number of largish cells, 
which have the appearance of nerve-cells (Fig. 85, g). - 

This extremely complex structure in a membrane which 
at first sight is so simple and so delicate, readily accounts 
for its being extremely difficult to ascertain with cer- 
tainty all the relations of its individual parts. It was 
one of the most important advances towards the know- — 
ledge of these relations which was made by the discovery 
of Heinrich Miiller, that namely from behind, from the 


988 | LECTURE XII. 


bacillar layer into the most anterior layers, a series of 
rows of fine fibres could be traced (radiating fibres, also 
called Miillerian fibres), which both receive the granules, 
and support the cones and rods (Fig. 85, B, C). This 
very complicated apparatus is placed as nearly as possible 
perpendicularly to the course of the fibres of the optic 
nerve. The greatest difficulty which exists with regard 
to the anatomical connection of the parts, is to determine 
whether the radiating fibres, either by bending directly 
round, or by a lateral anastomosis, become continuous 
with the optic or ganglionic fibres, and are thus them- 
selves nervous, or whether only an intimate apposition 
takes place, and so the nerves bear no other relation to 
the radiating fibres than those of proximity. A tactile 
body may also, you know, be either regarded as a body 
formed by a swelling of the nerve itself, or as a special 
structure up to which the nerve only proceeds or into 
which it enters. This question (of the connections of the 
radiating fibres) has not yet been definitively settled. At 
one time the probability became rather stronger that 
direct communications existed, at another that nothing 
more than a mere apposition took place. It can, how- 
ever, even now no longer be doubted, that this appara- 
tus is essential to the perception of light, and that the 
optic nerve might exist with all its parts without in any 
way possessing the power of receiving impressions of 
light, if it were not connected with this apparatus. Itis — 
well known that just that point in the background of the 
eye, where there are only optic fibres and no such appa- 
ratus, is the only one which does not receive impressions 
of light (the blind spot). In order therefore that the 
light may be rendered at all capable of acting upon the 
optic nerve, it unquestionably requires to be collected 
by means of this apparatus of fibres, and it is therefore 
an extremely interesting question for delicate physical 


THE PLEXIFORM DISTRIBUTION. - 989 


researches, whether the nerve itself receives at its ex- 
treme ends the vibrations of the waves of light, or 
whether another part exists, the oscillations of which act 
upon the optic nerve and produce a peculiar excitation 
in it. At all events there do ascend from the mem- 
brana limitans slightly curved fibres (Fig. 85, /), proba- 
bly connective tissue with its corpuscles, which afford a 
kind of stay or support to the whole apparatus (support- 
ing fibres [Stiitzfasern]), and are not, I should suppose, 
freely connected with the rest of it. 

We have, gentlemen, by the consideration of these re- 
lations brought out the fact, that the specific energy of 
individual nerves does not so much depend upon the pe- 
culiarity of the internal structure of their fibres as such, 
but that a great deal must be attributed to the special 
terminal arrangement, with which the nerve is connected, 
either directly or by contact, and from 
which the different nerves of sense de- eis 
rive their peculiar powers. If for exam- 
ple we examine a transverse section of 
the optic nerve external to the eye, it 
offers no peculiarities as compared with 
other nerves, which could at all account 
for this particular nerve’s being better 
able to conduct light than other nerves, 
whilst on the other hand the peculiar 
manner in which its extreme ends are 
distributed sufficiently explains the un- 
usually great sensitiveness of the retina 
to light. 

With regard to the terminations of 
nerves, there is still one mode to be men- 
tioned ; the plexiform distribution. This 


Fig. 86. Division of a primitive nerve-fibre at ¢, where we find a constriction; 
b’, 6” branches. a, Another fibre, crossing the former one. 300 diameters. 


19 





290 LECTURE XII. 


is a point to which more recent researches have been 
principally directed by Rudolph Wagner, inasmuch as 
this inquirer instituted investigations into the distribu- 
tion of the nerves in the electrical organ of fishes, and 
in so doing gave the chief impulse to the doctrine of the 
ramification of nerve-fibres. Up to that time nerves had 
been regarded as continuous, single tubes, which re- 
mained single throughout the whole of their course from 
a nervous centre to their termination. At present we 
know that nerves are distributed like vessels. Now see- 
ing that nerve-fibres directly divide, usually dichoto- 
mously, and their branches again divide and subdivide, 
extremely abundant ramifications may in this way in 
time arise, the import of which is extremely different, 
according as the nerve is motor or sensitive, and either 
collects impressions from, or diffuses motor impulses Zo, 
a considerable extent of surface. A truly marvellous 
instance has lately come to our knowledge in the electri- 
cal nerve of the electrical silurus (malapterurus), which 
has become so celebrated by the interesting experiments 
of Dubois-Reymond. Here Bilharz has shown that the 
nerve which supplies the electrical organ is in the first in- 
stance only a single microscopical primitive fibre, which 
keeps continually dividing until it finally resolves itself 
into an enormously great number of ramifications which 
spread themselves out upon the electrical organ. Here 
therefore the nervous influence must all at once diffuse 
itself from one point over the whole extent of the elec- 
trical plates. | 

In man we are still in want of distinct evidence with 
regard to this question, because the immense distances, 
over which individual nerves extend, render it almost 
impossible to follow any single given primitive fibres 
from their central origin to their extreme peripheral ter- 
mination. But it is not at all improbable that in man 


NERVOUS PLEXUSES. 291 


too analogous arrangements exist in some organs, 
although perhaps not such striking ones. If we compare 
the size of the nervous trunks in certain parts with the 
total number of operations which are effected in an - 
organ, for example, in a gland, it can scarcely appear 
doubtful that at least analogous arrangements exist there 
also. This mode of distribution offers peculiar interest 
in this respect, that many parts which are separated by 
intervals of space are thereby connected with one an- 
other. The electrical organ is composed of a number of 
plates, but not every plate is supplied with nerves pro- 
ceeding from the centre and intended only for it. The 
silurus does not set one or other of its plates in motion, 
but is obliged to set the whole of them in motion ; it is 
quite unable to divide the action. It can increase or 
diminish the intensity, but must always call the whole 
into operation. If in like manner we consider the ar- 
rangements which prevail in certain muscles, we find 
there is no evidence to justify us in assuming that every 
portion of a muscle receives special, independent nerve- 
fibres. On the contrary, a special division of nervous 
action in muscles only exists to a very limited extent, as 
we know from our experience in our own bodies. The 
neuro-pathological doctrines would lead us to infer that 
the will, or the soul, or the brain is able by means of spe- 
cial fibres to act upon every single part, but in reality 
this is by no means the case, for the nervous centres 
- have mostly only one single path by which they can 
communicate with a certain number of similar element- 
ary apparatuses. 

Now with regard to nervous plexuses, we are at the pre- 
sent time acquainted with most extensive arrangements 
of the kind in man, in the submucous tissue of the intes- 
tines, where the relations have recently been more closely 
investigated, in the first instance by Meissner and after- 


292 LECTURE XIL 


wards by Billroth. The submucous layer of the intes- 
tines is therefore, as Willis long ago declared it to be, a 


Fig. 87. 


SAH 
Se oth 





nervous tunic. On following up the afferent nerves, they 
are seen, after having divided, at last to break up into 
real networks ; these in new-born infants present at cer- 
tain points very large nodules, from which the nerve- 
fibres spread out into interlacements, so that a certain 
resemblance is thereby produced to a network of capil- 
laries. 

To what extent such arrangements prevail in the body 
generally has not yet been determined ; for these facts 
also are almost entirely new, and have only recently 
attracted the attention of observers, but probably the 

Fig. 87. Nervous plexus from the submucous tissue of the intestinal canal of a 
child, from a preparation of Herr Billroth’s. 2, n,n. Nerves which unite to form a 
network, and exhibit at their points of junction glanglioniform swellings abounding 


in nuclei. %, v. Vessels, and in the intervals nuclei belonging to the connective 
tissue. Magnified 180 diameters. 


NERVE-PLEXUSES—INTESTINES. + 993 


number of these nervous membranes will eventually be 
augmented. In order, however, to avoid any misunder- 
standing, I must at once add that these plexiform expan- 
sions are by no means simple, but that the large nodules 
I have mentioned have the appearance of ganglions, so 
that we have here in some sort new nervous centres pre 

senting themselves, and affording the possibility of a 
reinforcement of, or obstruction to, the original impulses. 
For the functions of the part this arrangement is mani- 
festly of great importance, for we should not well be able 
to explain the peristaltic movements of the intestinal 
canal, if some contrivance did not exist by which stimuli, 
that in the first instance were conveyed only to one spot 
in the canal, could be transferred from network to net- 
work and from part to part. The modes of distribution 
- of nerves, with which we were till recently acquainted, 
were not sufficient to afford anything approaching an ex- 
planation of the nature of peristaltic action, whilst these 
investigations of Meissner’s have at once furnished us 
with a most suitable groundwork for an interpretation of 
it. So much concerning the general forms which are, as 
far as we know at present, assumed by the pergvral 
terminations of the nerves. 

On the whole, these results correspond but little with 
the opinions which were formerly entertained, and with 
the hypotheses still advanced by the neuro-pathologists. 
The views of a neuro-pathologist of pure water amount, 
as is well known, to this, that a nervous centre is able, 
by means of nerve-fibres, to produce particular effects 
upon all, even the smallest, particles of the territory un- 
der its sway. Ifa mass of cancer or pus is to spring up 
in any little spot in the body, or merely a simple dis- 
turbance of nutrition to ensue, the neuro-pathologist re- 
quires a special arrangement, by means of which the 
nervous centre is enabled to have its influence conveyed 


294 LECTURE XII. 


into even the most minute districts of the periphery, and 
some route along which the messengers can travel who 
have been appointed to bear the order to the remotest 
points of the organism. Actual experience teaches us 
nothing of the kind. At those very spots where we 
know such an extremely complicated arrangement of the 
terminal apparatuses to exist, as I have described to you 
in the organs of sense, the nerves have no connection 
with the nutrition of the parts, and especially no demon- 
strable influence upon the elementary structures. In 
nearly all other places, either whole surfaces, or parts of 
organs are supplied with nerves in a uniform manner, or 
from these surfaces and parts of organs collective impres- 
sions are conveyed to the centres. In many parts con- 
cerning which we can certainly demonstrate that nervous 
influence is exercised upon them, as for example in mid- 
dle-sized and small vessels, we do not yet at all know to 
what extent their individual constituents receive special 
nerve-fibres. So bad are the anatomical foundations of 
the neuro-pathological doctrines. 


There still remains for us, gentlemen, now that we 
have discussed the terminal arrangements of the periphe- 
ral nerves, to consider the important series of nervous 
centres, or in a more restricted sense of the term, gangli- 
onc apparatuses. As I lately remarked to you, we find 
these predominating in those parts of the nervous centres 
in which there is grey matter. Still the mere grey hue 
of a part is not decisive proof of its ganglionic nature ; 
and in particular we must not suppose that the ganglion- 
cells are at all essentially concerned in the production of 
the grey colour, seeing that we find grey matter in many 
places where ganglion-cells do not exist. Thus, the most — 
external layer of the cortex of the cerebrum does not 
contain any well-marked ganglion-cells, although it looks 


NERVOUS CENTRES—GANGLION-CELLS. } 295 


grey; but we find there a translucent connective sub-— 
stance, pervaded by a large number of delicate vessels, 
and assuming, in proportion as these are more or less 
full, at one time more a reddish grey, at another more a 
whitish grey hue. On the other hand it frequently hap- 
pens that, where there are ganglion-cells, the substance 
really does not look grey, but has a positive colour vary- 
ing between brownish yellow and blackish brown. Thus 
we find spots in the brain, which have long been known 
by the names of substantia nigra, fusca, etc., in which the 
black or brown colour, which we perceive with the naked 
eye, is dependent upon the ganglion-cells, which form 
really coloured points. 

This coloration appears only in the course of years. 
The older an individual becomes, the more conspicuously 
do the colours show themselves ; still under certain cir- 
cumstances pathological processes also seem to accelerate 
their manifestation. Thus in the ganglia of the sympa- 
thetic it is a striking phenomenon, that certain morbid 
processes, for example, typhoid fever, appear to exercise 
a powerful influence in producing an early deposit of pig- 
ment. Since the pigment however constitutes a rela- 
tively foreign mass in the internal economy of the gan- 
glion-cells, and is not, as far as we know, subservient to 
their proper functions, but has all the characters of an 
inert accidental deposit, it may really be quite possible 
that these conditions should be regarded as a kind of 
premature senescence in the ganglia. In these cases we 
discern in the ganglion-cells (Fig. 88, @) in addition to the 
very distinct, large nucleus with its large, bright nucleo- 
lus, the contents properly so-called, which consist of a 
finely granular substance, and at a certain spot enclose 
the pigment which is generally deposited excentrically, 
but sometimes around the nucleus. Under certain cir- 
cumstances this deposit increases to such an extent that 


296 LECTURE XII. 


a great part of the cell is filled up with it. The more 
abundant it is, the darker does the whole spot appear to 
the naked eye. 

Formerly it was imagined that the majority of ganglion- 
cells were merely round bodies, but 
the conviction has been gradually 
gaining strength, that this form is an 
artificial one, and that the real state 
of the case is rather, that processes 
strike out from the cell in various 
directions, and ultimately become 
continuous with nerves or other 
ganglion-cells. These processes are 
in the first instance pale, and even where their transition 
into ordinary, darkly-contoured nerve-fibres can be 
traced, they are observed (but generally not until a cer- 
tain distance from the ganglion-cell) to become thicker 
and gradually to provide themselves with a medullary 
sheath. This circumstance which was formerly unknown 
explains how it was, that during so long a period so 
much obscurity prevailed with regard to these conditions. 
In the first part of their course, therefore, the processes 
of the glanglion-cells, especially in the brain and spinal 
marrow, are not nerves in the ordinary meaning of the 
word, but pale fibres which frequently bear scarcely any 
resemblance to the non-medullated fibres I have already 
described to you, and have rather the appearance of pale 
axis-cylinders (Fig. 88, a, 6). 

It was long believed that essential differences existed 
between the ganglion-cells according as they belonged to 
one or other of the three principal divisions of the 


Fig. 88. 





Fig. 88. Elements from the Gasserian ganglion. a. Ganglion-cell with nucleated 
sheath, which is prolonged around the efferent nerve-process; in the interior, the 
large, clear nucleus with its nucleolus, and round about it an accumulation of pig- 
ment. 6. Isolated ganglion-cell with a pale process proceeding up to it. c. Deli- 
cate nerve-fibre with pale axis-cylinder. 300 diameters. 


GANGLION-CELLS IN THE SPINAL CORD. 297 


nervous system, and therefore especially between the 
cells of the sympathetic and those of the brain and spinal 
marrow. But in this point also the contrary has proved 
to be the case, especially since Jacubowitsch has brought 
to our knowledge the new fact, of the correctness of 
which I have fully convinced myself, namely, that struc- 
tures which are perfectly analogous to the ordinary gan- 
glion-cells of the sympathetic, also occur in the middle 
of the spinal marrow and several parts which are consi- 
dered to belong to the brain. It may therefore be said, 
that cells belonging to the sympathetic nerve, concerning 
which it has already long been known that a great part 
of its fibres have their origin in the spinal marrow, are 
really also met with in the spinal marrow, and that in this 
respect also the cord does not form a simple and neces- 
sary contrast to the main trunk of the sympathetic. 

If we examine the spinal marrow, which affords the 
clearest representation of the plan of a true nervous cen- 
tre in the narrowest meaning of thé word, a little more 
closely, we everywhere find in its grey substance (the 
horns), and indeed in nearly every transverse section, 
different kinds of ganglion-cells. Jacubowitsch has, and 
I believe him to be in the main correct, distinguished 
three different forms, of which he calls the one motor, 
the second sensitive, and the third sympathetic. These 
lie generally in separate groups. 

I shall revert to this subject when I come to speak 
more at length concerning the spinal marrow; here I 
only wish to speak about the different forms of ganglion- 
cells. The so-called unipolar forms, are, in proportion 
as the examinations are conducted with more care, con- 
tinually becoming more and more rare. In the great 
nervous centres most of the cells possess at least two pro- 
cesses, and very many are multipolar or, more accurately, 


298 LECTURE XII. 


Fig. 89. 














MOTOR, SENSITIVE AND SYMPATHETIC CELLS. 299 


many-branched (polyclonous).* A multipolar cell is a 
body with a large nucleus, granular contents and, if it 
be particularly large, a spot of pigment, and is provided 
with processes running in different directions. These 
processes often divide into twigs and thus commences the 
condition of which I have already spoken (p. 290), that 
whole masses of filaments or fibres proceed from one 
point—a condition which indicates, that, in the first in- 
stance indeed according to circumstances, one path or 
another can be made use of, but that, when once a path 
has been chosen leading in the direction of the periphery, 
the impulse must be propagated in a relatively equable 
manner throughout the whole series of ramifications. 
These multipolar forms (Fig. 89, A) are mostly compara- 
tively large, and lie accumulated in those parts which 
are subservient to the motor functions! and they there- 
fore may be briefly designated motor cells. 

Those forms which correspond to the sensitive spots 
(Fig. 89, B) are usually smaller and do not present such 
an extraordinary luxuriance of ramification as the larger 
ones. A large portion of them possess only three, or 
perhaps, four branches. Those which Jacubowitsch has 
called sympathetic are, on the other hand again, larger, 
but have still fewer branches and are distinguished by a 
greater roundness of shape. These are differences which 
are certainly not so decided, as to enable us already at 
once to determine in every single case from the appear- 
ance of a ganglion-cell to which category it belongs ; but 
still, if we consider the individual groups, they are so 

Fig. 89. Ganglion-cells from the great nervous centres; A, B, C from the spinal 
cord, from preparations belonging to Herr Gerlach, D from the cortex of the cere- 
brum. A. Large, many-rayed cell (multipolar, polyclonous) from the anterior 
horns (motor cell). B. Smaller cells with three large processes, from the posterior 
horns (sensitive cells), ©. Two-rayed (bipolar, diclonous), more rounded cell, 


from the neighbourhood of the posterior commissure (sympathetic cell). 800 dia- 
meters. : 


* KAoY, wric, a shoot, twig.—Tr. 


300 LECTURE XII. 


striking, as to incite the observer to reflection upon the 
different qualities of these groups. 

In the course of time probably further distinctions, 
perhaps even in the internal economy of these cells, 
will be detected, but at present nothing more can be 
stated concerning them. This is a very great and 
lamentable void in our knowledge, and a void which 
we now particularly feel, because this is just the place 
where we should have to discuss the pacific action of 
these different elements. But it must not be overlooked 
that these conditions are among the most difficult which 
are ever submitted to anatomical investigation, and that 
one’s endeavors to produce specimens of a character to 
convince one’s own eyes alone, nearly always fail, because 
it is scarcely possible to succeed in effecting a real isola- 
tion of the cells with all their processes and connections, 
and because, on account of the extraordinary fragility of 
these bodies, one is nearly always compelled to trace them 
out in hardened sections. When sections are made of 
structures which to a great extent are composed of fibres 
and in which these run in a longitudinal, a transverse, or 
an oblique direction, so that an interlacement is always 
presented to the view, it depends of course entirely upon 
a happy chance whether in a section the course of a sin- 
gle fibre can be followed up over a large space with a 
certain degree of distinctness. This difficulty can certainly 
be lessened by making the sections in all possible direc- 
tions and thus increasing the probability of at last stum- 
bling upon the direction followed by the divisions of a 
branch, but even then the obstacles still remain so great 
that one can hardly expect, ever to be able to take in at 
one view the whole of the ramifications and connections 
of a cell belonging to the great nervous centres, that is 
provided with at all a large number of branches. 

In this respect also the electrical organ of fishes has 


PROCESSES OF THE GANGI:ON-CELLS. 801 


become a particularly interesting subject for investiga- 
tion, inasmuch as the one fibre which supplies the organ 
has been traced back by Bilharz to a single central gan- 
glion-cell, which is so large that it can be dissected out 
with the naked eye. This ganglion-cell has also delicate 
offsets in other directions, but it has not hitherto been 
possible to determine their ultimate relations any more 
than we are able to obtain a definite notion of the minute 
anatomy of the human brain, and especially to discover, 
to what extent connections take place there between the 
different cells. By the investigations which have been 
instituted into the structure of the spinal cord, it has been 
shown to be extremely probable, that all the processes 
of the individual ganglion-cells do not become continu- 

ous with nerve-fibres, but that a part of them run to 
_ other ganglion-cells and thus establish a communication 
between the cells. Moreover at certain points, espe- 
cially in several parts of the surface of the drain, still 
finer processes are found, which proceed from ganglion- 
cells and are connected with peculiar, quite characteris- 
_ tic apparatuses (bacillar layer of the cerebellum and cere- 
brum), which offer the greatest resemblance to those in 
the retina, those extremely delicate, vibratory arrange- 
ments of the radiating fibres. 

The processes of the ganglion cells might therefore, I 
think, be divided into three categories ; genuine nerve- 
processes, ganglion-processes, and those of which the im- 
port is entirely unknown and which, it would seem, are 
connected with peculiar and altogether specific appara- 
tuses, concerning which it is for the present uncertain, 
whether they are to be regarded as the terminations of 
the nerves, or only as structures placed in apposition to 
them. 


ne Ch Ue eas 


APRIL 8, 1858. 


SPINAL CORD AND BRAIN. 


The spinal cord—White and grey matter—Central canal—Groups of ganglion-cells 
—White columns and commissures. 

The medulla oblongata and the brain—Its granular and bacillar layer. 

The spinal cord of the petromyzon and its non-medullated fibres. 

The intermediate substance (interstitial tissue) —Ependyma ventriculoram—Neuro- 
glia—Corpora amylacea, 


THE last time, gentlemen, I laid before you the results 
of the most recent observations concerning the nature and 
distribution of the ganglion-cells in the great nervous 
centres ; allow me now to dwell a moment upon that 
organ which serves as a type in the development of the 
vertebrate, and is at the same time the one whose struc- 
ture we can best take in at one view, namely, the spinal 
cord. 

The spinal cord presents, as is well known, and can 
with ease be seen by the naked eye in any transverse 
section, in different parts of its course, a different amount 
of white matter, though nearly everywhere the white 
matter predominates over the grey. This appears in 
transverse sections in the form of the well-known horns, 
which are distinctly marked off from the pure white of 


the rest of the mass by their sometimes pale grey, some- 
802 


SPINAL CORD—GREY. MATTER—CENTRAL CANAL. 808 


times reddish grey colour. Wherever then the substance 
appears white to the naked eye, it is essentially composed 
of real, medullated nerve-fibres, in which only here and 
there a few ganglion-cells are imbedded ; and indeed a 
large proportion of these fibres are of considerable breadth, 
so that the quantity of medullary matter is at certain 
points extremely large. 

The grey matter of the horns is the real seat of the 
ganglion-cells, but here too the grey colour is by no 
means to be entirely ascribed to the accumulation of 
ganglion-cells ; on the contrary, they never, as you will 
afterwards see, form more than a small portion of this 
matter, and the grey hue is chiefly due to there generally 
being in these parts no separation of that opaque, strongly 
refractive substance (myeline, medullary matter) which 
fills the white nerves. 

It is in the centre of the grey substance that, as Still- 
ing, especially, has shown, the central canal (canalis spi- 
nalis) actually exists, which had previously been so com- 
monly supposed to be present, and had also frequently 
been described as of constant occurrence, but of which 
nevertheless no one had ever previously been able to 
furnish a regular demonstration. In the case of the old 
observers, as for example Portal, their investigations were 
in every instance confined to a few pathological speci- 
mens, from which they derived all the information they 
possessed upon the subject, and from which they inferred 
in a somewhat arbitrary manner that the presence of a 
canal was the rule. 

This central canal is so minute that extremely success- 
ful sections are required in order that it may clearly be 
perceived by the naked eye. Usually nothing more than 
a rounded grey spot can be detected, which is distin- 
guished from the surrounding parts by its somewhat 
greater density. It is by microscopical examination 


304 LECTURE XIII. 


alone that we can detect in this spot the transverse section 
of the canal in the shape of a minute hole (Fig. 90, c, c), 
which, like nearly all the free surfaces of the body, is in- 
vested with a layer of epithelium. It has now taken up 
its stand as a really regular, constant and persistent ca- 
nal. It is continued throughout the whole extent of the 
spinal marrow from the filum terminale, where it cannot 
at all times be very distinctly demonstrated, up to the 
fourth ventricle, where the orifice by which it opens into 
the so-called sinus rhomboidalis* is situated in the gela- 
tinous substance of the calamus scriptorius. Here it may 





iP 


Fig. 90. The half of a transverse section from the cervical part of the spinal mar- 
row. fa. Anterior fissure; fp, posterior fissure. cc. Central canal with the 
central thread of ependyma. ca. Anterior commissure with nerve-fibres crossing 
one another ; cp, posterior commissure. ra. Anterior roots; rp, posterior ones. 
gm. Accumulation of motor cells in the anterior horns; gs, sensitive cells of the 
posterior horns; gs’, sympathetic cells. The black, dotted mass represents a trans- 
verse section of the white substance of the cord (the nerve-fibres belonging to the 
anterior, lateral and posterior columns) and its lobular divisions. 12 diameters. 


* A name given to the floor of the fourth ventricle. 


WHITE MATTER OF THE SPINAL CORD. 305 


in the first instance be traced as a direct continuation 
from the floor of the fourth ventricle into a minute fun- 
nel-shaped fissure or line. 

As for the ganglon-cells, they are generally found in 
the largest number in the anterior and lateral parts of 
the anterior horns. It is at this spot that we chiefly meet 
with the large many-rayed corpuscles which we consi- 
dered the last time—corpuscles, which have in great part 
been traced into efferent nerves of the anterior root, and 
therefore give origin to motor nerves. 

An analogous, but less distinctly grouped accumulation 
is found in the direction of the posterior horns, but there 
the cells are rather the small, many-rayed ones, such as 
those I lately described to you ; they are connected with 
the fibres which run into the posterior root, and are 
therefore prebably subservient to the functions of sensa- 
tion. Besides, there is generally a third, sometimes more 
closely aggregated, at others more scattered, group of 
cells to be seen, which in their whole conformation re- 
mind us of the familiar cell-forms we meet with in the 
ganglia (Figs. 89, C; 90, gs’). Their special position in 
the spinal marrow is certainly not so clearly defined as 
that of the other parts ; perhaps they should be regarded 
as the origin of the sympathetic roots which run from the 
spinal marrow to the main trunk of the sympathetic, but 
this is as yet by no means clearly made out. 

In the white substance of the anterior, lateral and pos- 
terior columns are found the medullated nerve-fibres, 
which in general follow an ascending or descending 
course, so that in transverse sections of the spinal mar- 
row we scarcely gain sight of anything else than trans- 
verse sections of the nerve-fibres. Under the microscope 
therefore we generally see dark points, every one of 
which corresponds to a nerve-fibre. The whole mass of 


fibres constituting the columns of the spinal cord is, from 
20 


306 LECTURE XIII. 


within outwardly, split up into a series of groups or seg- 
ments chiefly following a radiating arrangement, or in 
some sort into wedge-shapes lobules, in consequence of a 
sometimes smaller, sometimes larger quantity of connec- 
tive tissue with vessels pushing its way in between the 
separate divisions, which are of a fascicular nature like 
those of the peripheral nerves. This connective tissue is 
directly connected with the more abundant mass of it 
present in the grey matter. Now with regard to the 
nerve-fibres themselves, it is probable that a certain num- 
ber of them proceed throughout the whole length of the 
spinal marrow, but it ought certainly not to be assumed 
that they are all derived from the brain; a probably 
considerable portion no doubt have their origin in the 
ganglion-cells of the spinal marrow itself, and then bend 
round into the anterior or posterior columns. Besides, 
the conviction has more and more gained ground, that, 
both between the two halves of the spinal marrow and 
between the separate groups of ganglion-cells, direct 
communications, commissures, exist—fibres passing across 
from one cell to another and from one side to the other, 
some so as to cross with those of the opposite side (ante- 
rior commissure), and some so as to run in a straight and 
parallel direction (posterior commissure). 

With the help of these anatomical observations a no- 
tion, though indeed as yet a very unsatisfactory one, can 
be formed of the routes along which the different pro- 
cesses are carried on within the nervous centres. Every 
special function possesses its special elementary, cellular 
organs; every mode of conduction finds paths distinctly 
traced out for it. In general too, well-defined peculiari- 
ties in the structure of the individual nervous centres 
correspond to the differences of function, and particularly 
the posterior horns become gradually more and more 
strongly developed as we ascend ; and in proportion as 


BACILLAR LAYER OF CEREBRUM AND CEREBELLUM. 307 


this development proceeds, we see the medulla oblongata, 
the cerebellum and cerebrum, coming into view, whilst 
the motor parts withdraw more and more into the back- 
ground and ultimately almost entirely disappear. All 
nervous centres, the lowest as well as the most highly 
developed, are disposed upon an analogous plan ; the 
only thing which, at least as yet, can be regarded as an 
especially characteristic peculiarity of the encephalon, is 
the circumstance, to which I called your attention in the 
last lecture, namely, that in the cerebrum and cerebel- 
lum processes from ganglion-cells are connected with par- 
ticularly complicated apparatuses, which most resemble 


Fie. 91. 


A 


Fig. 91. Diagrammatic representation of the disposition of the nerves in the cor- 
tex of the cerebellum, after Gerlach (‘ Mikroscopische Studien,’ plate L, fig. 3) 
A, White matter, 3B, C, grey matter, B, granular layer, Q, cellular layer. 


308 LECTURE XIII. 


the granular and bacillar layers of the retina (Fig. 91) 
which I have brought before your notice. For here too 
we find branched, almost arborescent filaments, which 
bear upon them minute granules, often in several rows, 
and attach themselves to the ganglion-cells in a manner 
essentially differing from, and much more delicate than 
that observed in the case of the proper nerve-processes. 
This kind of ganglion-cells may very likely stand in some 
close connection with the psychical functions, but at pre- 
sent we have no accurate information upon the subject, 
and it will, I expect, still be a longtime before anything 
positive can be made out about it, seeing that parts which 
are much more accessible to investigation, like the retina, 
present the very greatest difficulties to those who seek 
to discover the functions of the individual segments. 

The conformation which we have found to exist in the 
spinal marrow of man is essentially the same throughout 
the whole series of vertebrate animals, only that in man 
it is generally more complicated, and exhibits a greater 
abundance both of nerve-fibres and ganglionic matter. I 


Fig. 92. 





Fig. 92. Transverse section through the spinal marrow of Petromyzon fuviatilis. 
¥. Anterior fissure, #’’, posterior fissure, c, central canal with epithelium, gm, large 
many-rayed ganglion-cells with processes in the direction of the anterior roots, 
gp, smaller, many-rayed cells with processes running to the posterior roots, gs, large, 
roundish cells in the neighbourhood of the posterior commissure (sympathetic cells). 
n,n. Transverse sections of the large, pale nerve-fibres (Miullerian fibres), n’, gaps 
out of which the large nerves have gallen; mn”, gaps belonging to smaller fibres. 
Besides, the cut ends of numerous finer and coarser fibres. 


SPINAL MARROW OF THE LAMPREY. 309 


have brought you for comparison a section from the spi- 
nal marrow of one of the lowest of the vertebrate, namely 
the lamprey (petromyzon). In this animal the spinal 
marrow forms a very small, flat band which has some- 
what of a depression on the surface, and at first sight 
looks like a realligament. On making a transverse sec- 
tion of it, it is found to contain the same parts that we 
see in man, but all only in a rudimentary form. What 
in ourselves we call grey matter, is also found there on 
both sides in the shape of a flattened oblong lobe which 
contains a few scattered ganglion-cells, but only very 
few, so that perhaps only four or five are met with on 
each side of the transverse section. In the centre a cen- 
tral canal can likewise be detected, and that too lined 
with an epithelial layer similar to that which occurs in 
man. Below and in front of it generally lie a number of 
largish, round cavities, which correspond to unusually: 
large, non-medullated nerve-fibres (Fig. 93, @), which 
were first seen by Joh. Miller. Farther valence ile lie a 
few other thick fibres, but greatly exceeding these in num- 
ber a large quantity of very fine fibres which give the 
transverse section a very diversified, regularly dotted ap- 
pearance. Among the ganglion-cells three different kinds 
can here also be distinguished. Towards the outside of 

the grey matter lie many-rayed cells, larger anteriorly, 
smaller and more simple posteriorly. More internally 
and posteriorly on the other hand we find larger, more 
rounded, seemingly diclonous (bipolar) cells, comparable 
to the sympathetic forms. These cells communicate 
across the middle-line by means of real fibres, and be- 
sides we find processes which run out from the spinal 
marrow forwards and backwards and form the anterior 
and posterior roots. This is the simplest plan we have, 

displaying these relations ; it is the general type OF the 
anatomical structure of these parts. 


310 LECTURE XIII. 


A. circumstance worthy of particular observation here 
is that in the petromyzon, in the whole substance of the 
spinal marrow, no medullary matter exists in an isolated 
form, as is the case in man; we only find simple, pale 
fibres, which Stannius has without 
hesitation pronounced to be naked 
axis-cylinders. But without taking 
into account the fact that some of 
them have an enormous diameter, we 
find upon more accurate examination, 
as in the case of the gelatinous grey 
fibres in man, a membrane very 
clearly seen in transverse sections, 
especially after it has been coloured 
with carmine—and in the centre a 
finely granular matter, so that they 
seem rather to correspond to entire 
nerve-fibres. 

Hitherto, gentlemen, in considering the nervous sys- 
tem, I have only spoken of the really nervous parts of it. 
But if we would study the nervous system in its real rela- 
tions in the body, it is extremely important to have a 
knowledge of that substance also which lies between the 
proper nervous parts, holds them together and gives the 
whole its form in a greater or less degree. 

It is by no means very long ago since the existence of 
such interstitial masses of tissue was really only conceded 
in the case of peripheral nerves, and since the neurilemma 
was only traced back as far as the membranes of the spi- 
nal cord and brain, such an enveloping tissue being at 
most allowed to exist within the ganglia and in the sym- 
pathetic. In the nervous centres properly so called, and 


Fig. -98. 














Fig. 93. Pale fibres from the spinal marrow of Petromyzon fluviatilis. A. Broad, 
narrow, and extremely fine fibres. B. Transverse sections of broad fibres with a dis- 
tinct membrane and granular centre. 800 diameters, 


LINING MEMBRANE OF THE CEREBRAL VENTRICLES. 311 


especially in the brain, this interstitial matter of ours was 
regarded as essentially nervous, for a substance of the 
kind appeared a natural desideratum, as long as a direct 
transferrence of impulses from fibre to fibre was admitted 
to take place, as long therefore as the necessity for a 
real continuity of conduction within the nerves them- 
selves was not recognized. Thus in the brain a finely 
granular substance was spoken of as existing, which in- 
sinuated itself between the fibres, and though it certainly 
did not establish a complete connection between them, 
inasmuch as it occasioned a certain difficulty in the trans- 
ferrence of impulses, yet nevertheless seemed to rendcr 
a certain amount of conduction possible, so that when 
the impulse reached a certain degree of intensity, a 
direct transferrence from fibre to fibre could take place. 
This substance is however unquestionably not of a ner- 
vous nature, and if inquiry be made as to the relation 
which exists between it and the familiar groups of physi- 
ological tissues, it is impossible to doubt but that the 
substance in question is a kind of connective tissue ; and 
therefore an equivalent of that tissue with which we be- 
came acquainted in the shape of perineurium (p. 265). 
But the appearance of this substance is certainly very dif- 
ferent from that of what we call perineurium or neurilem- 
ma. These are comparatively firm, and often indeed hard 
and tough tissues, whilst the substance in questign is ex- 
tremely soft and fragile, so thatit is only with very great 
difficulty that we can succeed in making out its structure. 

I first had my attention directed to its peculiarities in 
investigations which I many years ago (1846) instituted 
into the nature of the so-called ning ‘membrane of the 
cerebral ventricles (Ependyma). At that time the view 
was generally held, which had been put forward first by 
Purkinje and Valentin, and afterwards especially by 
Henle, that a real lining membrane did not exist in the 


319 LECTURE XIII. 


ventricles of the brain, but only an epithelial covering, 
the epithelial cells directly resting upon the surface of 
the horizontally disposed nerve-fibres. This epithelial 
layer was what Purkinje called ependyma ventriculo- 
rum.* This assumption, it is true, was never shared in 
by pathologists. Pathological observation held on its 
course pretty unconcernedly by the side of these histolo- 
gical assertions. However, it appeared desirable that 
some understanding should be come to on the subject, 
since in a merely epithelial ependyma an inflammation 
would scarcely take place, like that which is wont to be 
attributed to serous membranes. The result of my in- 
vestigations was, that there certainly does exist a layer 
beneath the epithelium of the ventricles, which in many 
parts has quite the character of connective tissue, but in 
other places possesses great softness, so that it is ex- 
tremely difficult to give a description of its appearance. 
Every, even the slightest, traction of the part alters its 
appearance, and a substance now granular, now striated, 
now reticulated, now of any other form, is seen. 

At first I thought I had succeeded in showing that a 
tissue analogous to connective tissue did actually exist in 
this part, and that the presence of a membrane could be 
demonstrated. But, the more I occupied myself with 
the examination of it, the more did I become convinced 
that a real boundary between this membrane and the 
deeper layers of tissue did not exist, and that a mem- 
brane could only be spoken of improperly, inasmuch as 
the notion of a membrane involves the supposition that 
it is more or less different from the parts beneath it, and 
constitutes a separable object. Now in the present 


* This term kas had its signification extended by the Author, who takes it to 
include the whole of the layer (connective tissue as well as epithelium), which rests 
upon the nerve-fibres and is interposed between them and the cavity of the ventri- 
cles.—From a MS, Note by the Author. 


EPENDYMA OF THE VENTRICLES OF THE BRAIN. 813 


instance a separation of a rough kind may certainly not 
unfrequently be effected, but a more delicate kind of 
separation is altogether impossible. When the surface of 
any section of the ventricular wall is examined with a 
tolerably high power, the first thing noticed on the sur- 
face is an epithelium, sometimes in a better, sometimes 
in a worse state of preservation (Fig. 94, #). In the 
most favourable cases we find cylindrical epithelium with 
cilia, extending throughout the whole extent of the 
cavity of the spinal marrow (central canal) and of that 
of the brain (ventricles). Beneath this layer follows a 
sometimes more, sometimes less pure layer of a structure 
resembling connective tissue, which at first sight cer- 
tainly appears to be separated by a sharp outline from 


Fig. 94, 


HDQOOOQOQQOOQO® E 









ACY 











iy" 
i ae ANWAR 
& 










a= OL 
D5OLO © 
SSS 

OS) 





Fig. 94. Ependyma ventriculorum and neuro-glia from the floor of the fourth 
cerebral ventricle. Z, Epithelium, NV, nerve-fibres. Between them the free portion 
of the neuro-glia with numerous connective-tissue-corpuscles and nuclei, at » a ves- 
sel. In addition, numerous corpora amylacea, which are moreover represented 
separately at ca. 800 diameters, 


$14 LECTURE XIII. 


the deeper parts, for even with the naked eye, and espe- 
cially after the addition of acetic acid, an external grey 
and translucent layer is very distinctly seen, whilst the 
deeper layer looks white. This white appearance is due 
to the presence of medullated nerve-fibres which first 
occur singly, then continually become more numerous 
and closely aggregated, and as a rule run parallel to the 
surface. Thus it may certainly appear as if a particular 
membrane existed here, which could be separated from 
the uppermost nerve-fibres. But now, if we compare 
the substance which advances to the surface with that 
which lies between the nerve-fibres, no essential diffe- 
rence presents itself; on the contrary, it turns out that 
the superficial layer is nothing more than an extension 
upwards, beyond the nervous elements, of a portion of 
the interstitial tissue which is everywhere present be- 
tween them, but in this layer alone is seen in all its 
purity. The connection therefore is a continuous one. 
You see from this description that it was a very idle 
dispute, when it was discussed for years, whether the 
membrane which clothed the ventricles was a continua- 
tion of the arachnoid or pia mater, or was a special mem- 
brane. There is, strictly speaking, no membrane at all 
present, but it is the surface of the brain itself: which 
. directly meets the eye. In the case of articular cartilage 
also we must call it idle to dispute what kind of mem- 
brane invests the cartilage, since the cartilage itself ad- 
vances right up to the free surface of the joint. Neither 
is there any prolongation from the arachnoid or the pia 
mater to the surface of the ventricle ; the last processes 
which these membranes send inwardly are the choroid 
plexuses and the tela chorioides [velum interpositum]. 
Beyond these there is no serous covering found investing 
the internal surface of the ventricles of the brain. For 
this reason the conditions of the cerebral cavities cannot 


NEURO-GLIA—ITS CELLULAR ELEMENTS. 815 


be exactly compared with those of ordinary serous sacs. 
In the tela chorioides or the plexuses, a series of pheno- 
mena may certainly manifest themselves, which are pa- 
rallel to the diseases of other serous parts, but this can 
never take place in the same manner on the ventricular 
surface of the brain. 

This peculiarity of the membrane, namely, that it be- 
comes continuous with the interstitial matter, the real 
cement, which binds the nervous elements together, and 
that in all its properties it constitutes a tissue different 
from the other forms of connective tissue, has induced 
me to give it a new name, that of neuro-gla* (nerve- 
cement). The view that the substance in question be- 
longs to the class of connective tissues has recently been 
admitted on nearly all sides, but with regard to the ex- 
tent to which any isolated structures ‘that occur in it are 
to be considered as belonging to this substance, opinions 
are still divided. Even when I instituted my first spe- 
cial investigations into the structure of the ependyma of 
the brain and spinal cord, it turned out that certain stel- 
late cells which are met with in the middle of the spinal 
marrow (in the wall of the central canal, the existence of 
which was afterwards more accurately demonstrated, 
namely, in what I called the central thread of ependyma), 
and which up to that time had been regarded as nerve- | 
cells, unquestionably belonged to the neuro-glia. After- 
wards, and especially by the Dorpat school with Bidder 
at its head, a series of investigations were published, in 
which a great number of cells in the spinal marrow were 
set down as belonging to this connective tissue. Bidder 
himself was ultimately led to regard all the cells which 
are found in the posterior half of the spinal marrow, and 
therefore those sympathetic and sensitive cells also which 
you have just seen, as connective-tissue-corpuscles. On. 


* yAia, glue.—7r. 


316 LECTURE XIII. 


the other hand, Jacubowitsch has utterly denied the oc- 
currence of the cellular elements of connective tissue in 
any part of the brain or spinal cord, and has asserted 
that the interstitial tissue, which by him too, indeed, is 
regarded as connective tissue, is an altogether amorphous, 
finely granular or reticulated matter, which nowhere 
contains a single corpuscular element. Between these 
extremes, I think, we are perfectly justified by experi- 
ence in steermg a middle course. There can, according 
to my firm conviction, be no doubt but that the larger 
cells which pervade the posterior horns of the spinal mar- 
row are nerve-cells ; but, on the other hand, it must be 
maintained with equal positiveness, that, where neuro- 
glia is met with, it also contains a certain number of cel- 
lular elements. Immediately beneath the surface of the 
cerebral ventricles we commonly meet with spindle- 
shaped cells lying parallel to it, just like those which are 
found in other kinds of connective tissue ; these become 
larger under certain circumstances, and, in oblique sec- 
tions, often display themselves in the form of stellate 

cells (Fig. 94). 
A. substance altogether similar in structure to that, 
with which we have already become fa- 


F i ye eye ° e e e 
ee miliar in connective tissue—especially 
w b as far as its cells are concerned—is also 
© 5 
0 Ye found between the nerve-fibres of the 





07 cerebrum ; only the cells are so soft and 

fragile, that generally nothing but nu- 
clei can be perceived, scattered at certain intervals 
throughout the mass. On making a careful search, how- 
ever, even in fresh (not artificially hardened) specimens, 
soft cellular bodies of a roundish or lenticular form can 


Fig. 95. Elements of the neuro-glia from the white substance of the cerebral 
hemispheres of a human subject. a. Free nuclei with nucleoli, 6, nuclei with the 
granular remnants of the cellular parenchyma broken up in making the preparation, 
c, perfect cells. 800 diameters. 


PERINEURIUM AND NEURO-GLIA. 317 


be detected, which possess finely granular contents and 
large granulated nuclei with nucleoli, and lie, certainly 
in no very great number, between the nervous elements. 
At certain spots it has indeed been hitherto impossible 
to draw a well-defined boundary-line between the two 
tissues, and especially so at the surface of the cerebel- 
lum and cerebrum, between the granules which I have 
already (p. 307) described to you as connected with large 
ganglion-cells, and the nuclei of the connective tissue. 
Wherever the parts are seen severed from their connec- 
tions, it is not easy to make the distinction, and a posi- 
tive decision is only possible as long as the parts are 
viewed in their natural position. 

Now it is certainly of considerable importance to know 
that in all nervous parts, in addition to the real nervous 
elements, a second tissue exists, which is allied to the 
large group of formations, which pervade the whole body, 
and with which we have in the previous lectures become 
acquainted under the name of connective tissues. In 
considering the pathological or physiological conditions 
of the brain or spinal marrow, the first point is always to 
determine how far the tissue which is affected, attacked 
or irritated, is nervous in its nature, or merely an inter- 
stitial substance. We thus obtain at the very outset the 
important criterion for the interpretation of morbid pro- 
cesses, that the affections of the brain and spinal marrow 
may sometimes be rather interstitial, at others rather 
parenchymatous, and experience shows us that this very 
interstitial tissue of the brain and spinal marrow is one 
of the most frequent seats of morbid change, as for ex- 
ample, of fatty degeneration. | 

Within the neuro-glia run the vessels, which are 
therefore nearly everywhere separated from the nervous 
substance by a slender intervening layer, and are not in 
immediate contact with it. The neuro-glia extends in 


318 LECTURE XIII. 


the peculiarly soft form, which it presents in the great 
nervous centres and particularly in the brain, only to 
those parts which must be regarded as direct prolonga- 
tions of the cerebral substance, namely to the higher 
nerves of sense. The olfactory and auditory nerves also 
contain interstitial substance of the same character, whilst 
in all the rest, and even in the optic nerve itself, an in- 
creasing mass of a tougher tissue displays itself, which 
assumes quite the character of perineurium. 
Perineurium and neuro-glia are therefore equivalent 
parts, the only difference being that the one is of a soft, 
medullary, fragile nature, whilst the other is akin to the 
well-known fibrous tissues. The neurilemma stands in 
the same relation to the perineurium that the membranes 
of the brain and spinal cord do to the neuro-glia. 
Wherever neuro-glia exists, a very singular peculiarity 
presents itself which it has as yet been impossible to 
explain either chemically or physically, namely, that in 
every such case those peculiar bodies may be met with, 
which even in their structure remind one of granules of 
vegetable starch, whilst in their chemical reactions they 
altogether correspond to them—the much discussed cor- 
pora amylacea (Fig. 94, ca). They are found to the 
greatest extent and in the greatest numbers in the epen- 
dyma of the ventricles and spinal canal, and are the 
more abundant the greater the thickness of the ependyma. 
In many places but very few of them are found, whilst 
in others again their numbers increase so greatly, that 
the whole thickness of the ependyma is filled with them 
to such a degree, that it looks as if a pavement were be- 
fore one. They display themselves, however, strangely 
enough, in pathological conditions also, frequently in 
great numbers, when, in consequence of some disturb- 
ing cause, the quantity of neuro-glia becomes increased 
in proportion to that of nervous substance, as for 


CORPORA AMYLACEA. 319 


example after atrophic processes. In tabes dorsalis, as 
one used to say, or the atrophy of single columns of the 
cord, as we now usually interpret the old expression, we 
find, in proportion as the atrophy progresses, and the 
nerves in certain directions perish—cuneiform segments, 
in which the substance up to that time white becomes 
from without inwards grey and translucent—there being 
apparently a production of grey matter. This degene- 
ration is most frequent in the posterior columns, gene- 
rally in the immediate vicinity of the posterior fissure, 
and here it may go on, and generally does go on, in such 
a manner that the wedge penetrates deeper and deeper 
and at the same time increases in width. In these parts 





then the whole substance of the medullated fibres gradu- 
ally disappears, and distinct nerves are no longer disco- 
verable—the whole spot generally consisting of neuro-glia 
with an enormous accumulation of corpora amylacea. 
Nowhere in the body has there as yet been found any- 
thing completely analogous to structures of this sort, ex- 
cepting, as I have said, in those parts which appear to 
be direct protrusions of the cerebral substance, namely 
in the higher organs of sense, in the case of which origi- 
nally a certain quantity of central nervous matter entered 
into the sensorial capsules (Sinneskapseln) of the embryo. 
In the cochlea too, and the retina, bodies occur, which 


Fig. 96. Section of the spinal marrow in partial (lobular), grey or gelatinous atro- 
phy (degeneration). /. Posterior longitudinal fissure, s, s posterior, m,m anterior 
nerve-roots, communicating with the grey substance of the horns. In <A a slighter, 
in Ba more marked degree of atrophy, which is shown in the posterior columns 
around the central fissure f, and in the lateral columns at 7. Natural size. 


3920 LECTURE XIII. 


are allied to the corpora amylacea, although the chemi- 
cal tests have as yet only proved successful in the case 
of those found in the internal ear. 

When these bodies arg isolated, they exhibit in every 
respect such a complete analogy to vegetable starch that, 
long before I succeeded in discovering the analogy in 
chemical reaction, Purkinje had already introduced the 
term corpora amylacea on account of the morphological 
resemblance. You are no doubt aware, that the chemi- 
cal correspondence has in many quarters been doubted ; 
the late Heinrich Meckel especially had great doubts 
upon the subject, and supposed them to have a greater 
affinity to cholesterine. In more recent times, however, 
the matter has been investigated even by professed 
botanists, and every one who has bestowed close atten- 
tion upon it, has as yet acquired the same conviction 
which I published as my own. Niageli pronounces these 
bodies to be really and truly starch. 

Morphologically, they present themselves either as per- 
fectly circular bodies with regular, concentric layers, or 
their centre is a little on one side; or we find twin 
bodies ; or again the bodies are more homogeneous, pale, 
with a dim lustre, like fatty substances. When they are 
cautiously treated with a dilute solution of iodine, they 
assume a pale bluish, or greyish blue colour, though a _ 
great deal certainly depends upon the proper degree of 
concentration of the test. If afterwards we very cau- 
tiously add sulphuric acid, we obtain, when the proper 
effect is produced, a beautiful blue, which is best shown 
by allowing the reagent to act very slowly. When sul- 
phuric acid acts violently upon them, a violet tint, which 
speedily becomes brownish red or blackish, is obtained, 
presenting a most decided contrast to the neighbouring | 
parts, which become yellow or at most yellowish brown. 


Eee PO Beh aed Ve 


APRIL 7, 1858. 


ACTIVITY AND IRRITABILITY OF CELLULAR ELEMENTS. 
DIFFERENT FORMS OF IRRITATION. 


Life of individual parts—The unity of the neurists—Consciousness—Activity of 
individual parts—Excitability (irritability) as a general criterion of life—Mean- 
ing of irritation—Partial death—Necrosis. 

Function, nutrition, and formation, as general forms of vital activity—Difference 
of irritability according to the different forms of activity. 

Functional irritability—Nerves, muscles, ciliated epithelium, glands—Fatigue and 
functional restitution—Stimuli—Their specific relations—Muscular irritability. 

Nutritive irritability—-Maintenance and destruction of elements-—Inflammation— 
Cloudy swelling—Kidney (morbus Brightii) and cartilage—Neuro-pathological 
doctrines—Skin, cornea—The humoro-pathological doctrines—Parenchymatous 
exudation, and parenchymatous inflammation. 

Formative irritation—Multiplication of nucleoli and nuclei by division—Multi- 
nuclear cells; medullary cells and myeloid tumours—-Comparison between for: 
mative muscular irritation and muscular growth—Multiplication (new forma- 
mation) of cells by division—-The humoro- and neuro-pathological doctrines. 

Inflammatory irritation as a compound phenomenon-—Neuro-paralytical inflamma- 
tion (Vagus, Trigeminus). 


I HAVE given you, gentlemen, a somewhat lengthy 
sketch of the histological arrangements of the body, in 
order to make the inference plain to you, which in my 
Opinion must be the starting point of all future conside- 
rations that are instituted concerning life and vital ac- 
tivity—that, namely, in all parts of the body a splitting 
up into a number of small centres takes place, and that 


nowhere, as far as our experience extends, does a single 
91 821 


822 LECTURE XIV. 


central point susceptible of anatomical demonstration 
exist, from which the operations of the body are carried 
on in a perceptible manner. And even if we appeal to 
the experience which every one daily stores up around 
him, we shall find that this is the only view which con- 
cedes life to the individual parts of an organism, or 
allows it to the plant—the only view which enables us 
to institute a comparison both between the collective 
life of the developed animal and the individual life of 
its smallest parts; and also between the life of a plant 
as a whole and the life of the individual parts of a 
plant. 

The opposite view which at this very moment is mani- 
festing itself with a certain degree of energy—that 
namely, which beholds in the nervous system the real 
central point of life—is met by this extremely great 
difficulty, that, in the very same apparatus, in which it 
places its unity, it again finds the same splitting up into 
an infinite number of separate centres, which is pre- 
sented by the rest of the body; and that in no part of 
the whole nervous system it can show the real central 
point, from which, as from a seat of government, man- 
dates are issued to all quarters. 

It may seem very convenient to say that the nervous 
system constitutes the real unity of the body, inasmuch 
as there is certainly no other system which enjoys such 
a complete dissemination throughout the most various 
- peripheral and internal organs. But even this wide dis- 
semination and the numerous connections which exist 
between the individual parts of the nervous system, are 
by no means calculated to show it to be the centre of all 
organic actions. We have found in the nervous system 
definite little cellular elements which serve as centres of 
motion, but we do not find any single ganglion-cell in 
which alone all movement in the end originates. The 


THE UNITY OF THE Spates CONSCIOUSNESS. 323 


most various individual motory apparatuses are connected 
with the most various individual motory ganglion-cells, 
Sensations are certainly collected in definite ganglion- 
cells, still among them too we do not find any single cell 
which can in any way be designated the centre of all 
sensation, but we again meet with a great number of 
very minute centres. 

All the operations which have their source in the 
nervous system, and there certainly are a very great 
number of them, do not allow us to recognise a unity 
anywhere else than in our own consciousness ; an ana- 

tomical or physiological unity has at least as yet been 
-nowhere demonstrable. If we really were to set 
down the nervous system with its numerous separate 
centres as the central point of all organic actions, even 
then the thing actually sought for, a real unity, would 
not have been obtained. If a clear idea is formed of 
the difficulties which stand in the way of such a unity, 
it can scarcely be doubted, but that we are continually 
led astray by the spiritual phenomena displayed in our 
own persons, in the interpretation of organic processes. 
Feeling ourselves to be something simple and indivisible, 
we always start with the presumption that. everything 
else must be regulated by this indivisible principle. 
But if we trace the development of any given plant 
from its first-germ up to the highest point in its evolu- 
tion, we meet with a series of processes altogether 
analogous, without our being able to entertain the suppo- 
sition for a moment, that such a unity exists in it, as we 
are led by our consciousness to suppose exists in us. 
Nobody has been able to detect a nervous system in plants ; 
in no case has it been discovered that the whole of the 
fully developed plant was governed from a single point. 
All the vegetable physiology of the present day is based 
upon the investigation.of the activity of cells, and if 


324 LECTURE XIV. 


violent opposition is still made to the introduction of the 
same principle also into the animal economy, there is, I 
think, no other difficulty in the way but the one, that s- 
thetical and moral scruples cannot be overcome. 

It cannot of course here be our business either to 
refute these scruples or to point out how they might be 
reconciled with the views I advocate. I have only to 
show in how great a degree the pathological processes 
which especially interest us, in all cases conduct us back 
to the same cellular principle, and how much they are 
in every case opposed to that notion of a single con- 
trolling principle, which is sought to be established by 
the neuro-pathologists. This opinion of mine has after 
all really nothing new or uncommon in it. If for thou- 
sands of years the life of the individual parts of the 
body has been talked about, if the position is admitted, 
that in diseased conditions the death of individual parts, 
necrosis or gangrene in them may take place, whilst the 
whole still continues to exist—the inference is, . that 
something of our way of thinking had long been ex- 
pressed in the views held by the world in general: only 
people had not formed very clear notions upon the subject. 
If we speak of the life of the individual parts of a 
body, we must also know in what way life manifests 
itself, and whereby it is essentially characterized. This 
characteristic we find in actevity, an activity indeed, in 
which there is displayed by every single part, whilst it - 
contributes its contingent, according to its peculiarities, 
to the general activity of the body—something identical 
with the life of the other parts ; for else we should be in 
no way justified in regarding life as something in every 
case similar, and derivable from some common origin. 

This vital activity is, as far at least as we are able to 
judge, nowhere, in no part whatever, carried on by 
means of any cause allotted to it from the very begin- 


IRRITABILITY. 325 


ning, and entirely confined to it, but we everywhere see 
that a certain ezcitation is necessary for its production. 
Every vital action presupposes an excitation, or if you 
like an ¢trretation. The ¢wrritability of a part, therefore. 
appears to us the criterion, by which we can judge 
whether it is alive or not. Whether, for example, a 
nerve be alive or dead, we cannot immediately deter- 
mine by an anatomical examination of it, conducted 
either microscopically or macroscopically. In the out- 
ward appearance, in the more obvious structural ar- 
rangements, which we are able to decipher by the aid 
of our auxiliaries, we rarely find sufficient to enable us 
to come to a decision upon a point such as this. © 
Whether a muscle is alive or dead, we are but little 
able to judge, inasmuch as we find its structure still 
preserved in parts which perished years ago. I found 
in a foetus, which, in a case of extra-uterine pregnancy, 
had lain thirty years in the body of its mother, the 
structure of the muscles as intact as if it had just been 
born at its full time. Czermak examined parts of 
mummies, and found in them a number of tissues which 
were ina state of such perfect preservation, that the 
conclusion might very well have been come to, that the 
parts had been taken from a living body. Our notion 
of the death, decease, or necrosis of a part, is based 
upon nothing more or less than this, that whilst its form 
_ is preserved, and indeed in spite of it, we can no longer 
' detect any irritability in it. This has been most. clearly 
shown quite recently in the course of some investigations 
into the mere hidden properties of nerves. Now that, 
by the investigations of Dubois-Reymond, activity has 
been shown to exist in nerves even when in a so-called 
state of repose, and that it has been discovered, that in 
a nerve, even when seemingly at rest, electrical pro- 
cesses are continually going on, and that it constantly 


826 LECTURE XIV. 


produces an effect upon the magnetic needle—now we 
are able, by means of this physical experiment, with 
certainty to judge when a nerve is dead, for, as soon as 
death has stepped in, those qualities cease, which are in- 
separably connected with the life of the nerve. 

This peculiarity which we find in some parts exhibited 
in such a marked degree and so evidently demonstrable, 
becomes less and less apparent, the more lowly the or- 
ganization of the part, and our criteria are least to be 
depended upon in the case of the class of connective 
tissues ; for we are, indeed, really frequently much puz- 
zled to decide whether a part composed of one of them 
is still alive or has already perished. 

If now we proceed with our analysis of what is to be 
included in the notion of excitability, we at once dis- 
cover, that the different actions which can be provoked 
by the influence of any external agency, are essentially 
of three kinds; and I consider it of great importance 
that you should pay particular attention to this point, as 
it will greatly assist you in the classification of patholo- 
gical conditions, and because it is not wont to be set forth 
with particular distinctness. 

When, namely, a given action is called into play, we 
have to deal with a manifestation either of the function, 
the nutrition, or the formation of a part. Tt certainly 
cannot be denied that at certain points the boundaries 
between these different processes disappear, and that 
between the nutritive and formative processes and also 
between the functional and nutritive ones, there are tran- 
sitional stages ; still, when they are typically performed, 
there is a very marked difference between them; and 
the internal changes which the individual excited part 
undergoes, according as it only performs its functions, or 
is subjected to a special nutrition, or becomes the seat 
of special formative processes, exhibit considerable dif- 


FUNCTIONS OF CELLS—CELL-CONTENTS, 327 


ferences. The result of an excitation, or if you will, an 
irritation, may, according to circumstances, be either a 
merely functional process; or the effect may be that a 
more or less increased nutrition of the part is induced 
without there necessarily being any excitation of its func- 
tions ; or a formative process may set in, giving rise to a 
greater or less number of new elements. These differ- 
ences manifest themselves with greater or less distinct- 
ness in proportion as the individual tissues of the body 
are more or less capable of responding to the one or other 
kind of excitation. When, namely, we speak of the 
functions of parts—in the case of a considerable num- 
ber of tissues the real functions shrink into a very small 
compass ; we are on the whole able to say but very little 
concerning the real functions, in the higher sense of the 
word, of nearly all the connective tissues, and of the 
great majority of epithelial cells. We are no doubt 
able to say what their use under particular circum- 
stances is, still they always rather appear to be rela- 
tively inert masses, which scarcely perform any real 
functions in the ordinary meaning of the word, but 
rather serve as supports to the body, or as coverings to 
the different surfaces, or, in other localities, according 
to circumstances, act as media of union, intervention, or 
separation. | 

The case is different, on the other hand, with those 
parts, which, owing to the peculiar nature of their inter- 
nal arrangement,. are liable to a more rapid change, 
such as the nerves, muscles, and muscular organs, glands 
and a few other structures, as, for example, among the 
epithelia, ciliated epithelium. In all these tissues, which 
are subservient to important functions, we find that 
these functions are chiefly due to very delicate changes 
of arrangement, or if you wish it expressed in more 
precise terms, to minute changes of place, in the minute 


328 | LECTURE XIV. 


particles of the internal matter, the cell-contents. In these 
cases therefore it is not so much the real cell in its pure 
form which decides the question, as the specific matters 
with which it is provided internally ; the chief agent is 
not so much the membrane or the nucleus of the cell, as 
the contents. It is these which, when exposed to cer- 
tain influences, become comparatively rapidly changed, 
without our being always able morphologically to de- 
tect any trace of a change in the arrangement of the 
contained particles. The utmost that we can observe in 
the shape of a palpable result is a real locomotion of 
small, visible particles, but we cannot push our analysis 
to such an extent, as to enable us to form any opinion 
as to the internal cause, in virtue of which this locomo- 
tion is effected by the ultimate particles which compose 
the cell-contents. When an excitation takes place in a 
nerve, we now know that a change in its electrical state 
is connected with it, a change which, from all that is 
known to us concerning electrical excitation in other 
bodies, must of necessity be referred to a change in the 
position which the individual molecules 
assume to one another. If we conceive 
€d585R the axis-cylinder to be made up of elec- 
ae "trical molecules, we can easily imagine 
@@GEG6 that every two of these molecules take 
up an altered position with regard to 

one another at the moment the stimulus is applied. Of 
these processes we see nothing. The axis-cylinder looks 
just as usual. If we watch a muscle during its contrac- 
tion, we remark, it is true, that the intervals which sepa- 
rate the individual so-called discs (p. 82) become shorter ; 
and as we now know that the substance of the mus- 


Fie. 97. 


Fig. 97. Ideal diagram of the condition of the molecules of a nerve when it is 
, at rest (in a peripolar state, A), or in an electrotonic (dipolar) state, B. From Lud- 
wig, ‘ Physiolog.,’ I, p. 108. 


FUNCTIONAL IRRITABILITY. : 829 


cle consists of a series of minute fibrils, which in their 
turn contain little granules at certain intervals corres- 
ponding to these discs, we conclude therefrom with some 
degree of assurance that really local changes take place 
in the minutest elements, though they cannot be further 
referred to any visible or directly recognizable cause. 
We cannot perceive any definite chemical change, or 
any alteration in the state of nutrition of the parts ; 
we only see a displacement, a dislocation of the parti- 
cles, which, however, probably depends upon some 
slight chemical change in the molecules composing them. 
-. In the case of ciliated epithelium you see how the 
fine cilia, which are seated upon the surface of the cells, 
move ina certain direction, and in this direction exercise 
a locomotory effect upon the little particles which come 
near to them. If we isolate the individual cells, we 
see that every one of them has at its upper end a bor- 
der of a certain thickness, from which little hair- 
shaped prolongations run out. These all move in such 
a way that a cilium which, whilst quiet, stands quite 
upright, bends forwards and then throws itself back- 
wards. But we are unable to perceive any changes 
within the individual cilia, by means of which the move- 
ment is effected. 

Just the same is the case with gland-cells, con- 
cerning which we-cannot entertain the least doubt that 
they produce a definite locomotory effect. For since 
Ludwig has shown in his researches on the salivary 
glands, that the pressure of the outward current of 
saliva is greater than that of the inward stream of blood, 
the only conclusion that is left us is, that the gland-cells 
exercise a definite motor influence upon the fluid; and 
that the secretion is driven out with a definite force, 
which is not due to the pressure of the blood; or any 
special muscular action, but to the specific energy of the 


330 LECTURE XIV. 


cells as such. Still we are just as little able to discern 
in a gland cell, whilst performing its functions, that its 
constituent particles are engaged in any peculiar material 
process, as we were in the case of the nerves, or ciliated 
epithelium. 

These facts derive great support from the circumstance 
that we are able to perceive, that the functional activity 
of individual parts does experience a certain amount of 
impairment, if it is continued for too long a time. In 
all parts certain states of fatigue manifest themselves, 
states, during which the part is no longer able to origi- 
nate the same amount of movement, that up to that 
time could be perceived in it. But, in order that they 
may again become compétent to perform their functions, 
these parts by no means always require a new supply of 
nutriment, a fresh absorption of nutritive material ; rest 
alone is sufficient to enable them to resume their activity 
in a short space of time. A nerve, which has been cut 
out of the body; and used for experiment, after a cer- 
tain lapse of time becomes incapable of discharging its 
functions ; but if it be allowed to repose under favour- 
able circumstances, which prevent it from drying up, it 
gradually regains its powers. This restetution of func- 
tional power (functional restitution), which takes place 
without any proper nutritive action, and in all proba- 
bility depends upon the circumstance, that the mole- 
cules which had quitted their usual position gradually 
revert to it—we can produce in different parts by 
means of certain stimuli. According to the views of 
the neuro-pathologists these stimuli would only act 
upon the nerves, and through the medium of the nerves 
upon the other parts; but with reference to this very 
point we have some facts which cannot well be explained 
in any other way than by the assumption, that an in- 
fluence is really exercised upon the parts themselves. 


FUNCTIONAL IRRITATION. 331 


If we take a single ciliated cell, and, after entirely 
isolating it from the body, allow it to swim about, and 
wait until a state of complete repose has declared itself, 
we can again call forth the peculiar movements of its 
cilia by adding a small quantity of potash or soda to 
the fluid, a quantity not large enough to produce corro- 
sive effects upon the cell, but sufficient, upon penetra- 
tion into it, to induce a certain change in its contents. 
A peculiarly interesting fact, however, is that the num- 
ber of substances which will act, as stimuli, upon ciliated 
epithelium, is limited to these two. This explains how 
it happened that Purkinje and Valentin (who, it is well 
known, first made experiments, and those upon a very 
extensive scale, upon ciliary movement), although they 
experimented with a very large number of substances, 
at last, after they had tried all sorts of things—mechan- 
ical, chemical and electrical stimuli—came to the con- 
clusion that there was no stimulus whatever, which 
could provoke the ciliary movement. I had the good 
fortune incidentally to stumble upon the peculiar fact, 
that potash and soda are such stimuli. Here we cer- 
tainly cannot call in any nervous influence to our aid, 
and such influence appears to be the less admissible for 
the reason that, in accordance with the well-known ex- 
periments, the ciliary movement is maintained in the 
dead body at atime when other parts have already be- 
gun to putrefy. The ciliated epithelium of the frontal 
sinuses and the trachea is found in human corpses in a 
state of perfect excitability thirty-six to forty-eight 
hours after death, when every trace of irritability has 
long vanished from the remainder of the body. _ 

Much the same is the case with all other excitable 
parts. We see nearly everywhere that certain excitants 
act more readily than others, and that many are totally 
incapable of producing any particular effect. Nearly 


339 - | LECTURE XIV. 


everywhere do we find specific relations or affinities to 
exist. If we cast our eyes upon the glands, it is a well- 
known fact that there are specific substances, by which 
we are enabled to act upon one gland, and not upon 
another ; to rouse the specific energy of one gland, 
whilst all the rest remain unaffected. In the case of 
glands it is certainly much more difficult to exclude the 
influence of the nerves, than in that of ciliated epithe- 
lium, still certain experiments are recorded, in which, 
after the section of all the nerves, say of the liver 
(G. Harting), it was found possible, by means of the 
injection of irritating substances into the blood (these 
being such as experience had shown to bear some inti- 
mate relation to the organ), to provoke an increased 
secretion in the organ. 

The discussion of this subject has, as you no doubt 
are well aware, recently chiefly become centred in the 
question of the irritability of muscle, a question which 
has proved so difficult for the very reason that the pos- 
session of irritability was restricted by Haller with great 
exclusiveness to muscle. Haller with the greatest ob- 
stinacy combated the opinion that any other part was 
irritable ; and curiously enough he even contested the 
irritability of parts, which, as the minuter investigations 
of later observers have shown, contain muscular ele- 
ments, as for example, the middle coat of the vessels. 
Indeed, he made use of tolerably energetic expressions 
when repudiating the excitability of the vessels, which 
even then was maintained by others. I have already 
informed you that there are large tracts in the vascular 
system (for example, in the umbilical vessels of the foe- 
tus, where they are particularly well marked) in which 
enormous accumulations of muscular fibres are found, 
but not a trace of any nerves. Here irritability exists 
ina high degree ; we can produce contractions of the 


NUTRITIVE IRRITABILITY. 333 


muscles mechanically, chemically and electrically. Just 
the same is the case with many other, small vessels, 
which by no means exhibit nerve-fibres in all their parts. 
In them too we can at every single point where muscles 
exist, at once provoke contraction. 

The solution of this question has recently, as is well 
known, been particularly promoted by the fact that, by 
the employment of certain poisons, especially the woo- 
rara poison, observers have succeeded in paralyzing the 
nerves right down to their extreme terminations, or at 
least as far as these were accessible to the experiment ; 
and this in such a manner, that the objection cannot 
well be raised, that the excitability of the extreme ter- 
minations of the nerves contained in the muscle is pre- 
served. The paralysis produced by the woorara poison 
is completely confined to the nerves, whilst the muscles 
just as completely retain their irritability. Whilst the 
most violent electrical currents were made to act upon 
the nerve in vain, without the production of the least 
_ movement, the slightest mechanical, chemical or electri- 
cal stimuli are sufficient to throw the muscle experi- 
mented upon into a state of excitation. 

I have mentioned these facts to you, in order that I 
might not be thought to treat the different divisions of 
my subject too unequally. The question of function, 
however, interests us less here. Nevertheless, you will 
be able to gather from what I have communicated to you, 
that now-a-days it can no longer be said with any show 
of reason that the nerves alone are irritable parts, but 
that we are irresistibly led to consider functional irritabi-, 
lity, at least, as a property belonging to whole series of 
organs. 

Far less known, gentlemen, is that clearly demonstra- 
ble series of processes in which nutritive irritability mani- | 
fests itself—that power possessed by individual parts of 


334 LECTURE XIV. 


taking up, when excited by definite stimuli, more or less 
matter and transforming it. This constitutes at the same 
time the first step in the most important processes which 
we have to follow into the domain of pathologico-anato- 
mical facts. 

A part, which nourishes itself, can in doing so either 
limit itself to a mere maintenance of its existence, or it 
may, as is especially seen in pathological cases, take up 
into itself a larger quantity of nutritive material than is 
wont to happen in the ordinary course of things. If we 
investigate these processes of absorption more closely, we 
always find that, as I have already had occasion to re- 
mark to you, the number of histological elements remains 
the same before and after the occurrence of the excita- 
tion ; and we thus distinguish simple hypertrophies from 
the hyperplastic conditions, to which, in their external 
effects, they often bear so great a resemblance (p. 94, 
Fig. 27, B). It is, however, of extreme importance for 
the attainment of correct pathological notions, that we 
should know that a part, which in virtue of some inhe- 
rent power, takes up a large quantity of material, need 
not on that account necessarily fall into a permanent 
condition of enlargement, but that on the contrary, under 
these very circumstances there often arises subsequently 
in its internal economy a disturbance which imperils the 
persistence of the part and becomes the proximate cause 
of its destruction. There are, as we know from experi- 
ence, certain limits to the enlargement of every tissue, 
within which it is able to maintain a regular existence ; 
if these limits be exceeded, and especially, if suddenly, 
we always see that obstacles spring up impeding the fur- 
ther life of the part, and that when the process runs a 
particularly acute course, a weakening of the part sets 
in, proceeding to a complete destruction of it. 

Processes of this kind form a part of that domain which 


CLOUDY SWELLING. 3835 


in ordinary life is assigned to inflammation. A number 
of inflammatory processes on their first appearance really 
exhibit nothing more than an increased assumption of 
material into the interior of the cells, entirely resembling 
what we find in simple hypertrophy. If, for example, 
we consider the history of Bright’s disease in its ordinary 
course, we constantly find, that the very first thing which 
can be detected in a kidney affected with this disease, 
consists in this, that in the interior of the uriniferous tu- 
bules whilst still quite intact, the individual epithelial 
cells which are, as is well known, even in their normal 
state tolerably large, become still larger. These epithe- 
lial cells which fill up the tubules are not only large, but 
at the same time also present a very 
cloudy appearance, inasmuch as a larger 
quantity of material than usual has 
everywhere been taken up into the cells. 
The entire uriniferous tubule is thereby 
rendered broader, and appears even to 
the naked eye as a convoluted, whitish, 
opaque body. If we isolate the indi- 
vidual cells, which is somewhat difficult, 
as the cohesion of the particles compos- 
ing them has usually begun to suffer, we find in them a 
granular mass apparently containing nothing else than 
the granules which are normally present in the interior 
of the cells, but which accumulate in greater numbers the 
- greater the energy with which the process is carried on, 
so that even the nucleus gradually grows indistinct. This 
is the condition of cloudy swelling (triibe Schwellung), as 
it is met with in many irritated parts, as an expression 


Fie. 98. 





Fig. 98. Convoluted urinary tubule from the cortex of the kidney in morbus 
Brightii. a. Tolerably normal epithelium, 6, state of cloudy swelling, c, com- 
mencing fatty metamorphosis and disintegration. At b and c increased breadth of 
the tubule. 300 diameters. 

* 





336 : LECTURE XIV. 


of the irritation which attends many forms of what is 
called inflammation. From these processes backwards to 
the phenomena of simple hypertrophy we find no recog- 
nizable boundaries at all. We cannot at once say, when 
we meet with a part enlarged in this way, and contain- 
ing a greater amount of matter than usual,-whether it 
will retain its life or perish ; and therefore it is extremely 
difficult in very many cases, when nothing at all is known 
concerning the process through which such a change has 
been produced, to distinguish simple hypertrophy from 
those forms of inflammatory processes which are essen- 
tially accompanied by an increased absorption of nutri- 
tive material. 

In these processes too it is scarcely possible to refuse 
the individual elements, when incited by a stimulus 
directly applied to them, the power of taking up an 
increased quantity of material ; at least it is opposed to 
all the results of experience, to assume that such an in- 
creased absorption must be due to a special innervation. 
If we select a part which, in accordance with all observa- 
tion, is entirely destitute of nerves, as for example, the 
surface of an articular cartilage, we can, as was shown 
many years ago by the beautiful experiments of Redfern, 
produce altogether similar effects by means of direct 
stimuli. In precisely the same way, there are not un- 
frequently observed, in chronic diseases of cartilage, no- 
dular elevations of the surface ; and upon examining 
such spots microscopically we find the same thing that I 
showed you in a former lecture in a costal cartilage 
(p. 48, Fig. 9), namely, that the cells which at other 
times are very delicate, small, lenticular bodies, increase 
in size, swell up into large, round corpuscles, and in pro- 
portion as they take up more matter, enlarge in all direc- 
tions, so that at last the whole spot forms a little protu- 
berance above the surface. Now in articular cartilage 


DIRECT IRRITATION OF TISSUES. 337 


“no nerves at all are found ; the terminal ramifications of 
those nearest to it are at best situated in the medulla of 
the bone immediately adjoining, and that, perhaps, is 
separated from the irritated spot of the surface by an in- 
tact, intervening layer of cartilaginous tissue one or two 
lines in thickness. Now it would indeed be contrary to 
all experience to conceive that a nerve could from the 
medulla of the bone exercise a special action upon the 
cells of the surface of the cartilage, which were the seat 
of irritation, without a simultaneous affection of the cells 
lying between the nerve and the irritated spot. If we 
draw a thread through a cartilage, so that merely a trau- 
matic irritation is produced, we see that all the cells 
which lie close to the thread become enlarged through 
an increased absorption of material. The irritation pro- 
duced by the thread extends only to a certain distance 
into the cartilage, whilst the more remote cells remain 
altogether unaffected. Such observations cannot be ex- 
plained otherwise than by assuming that the stimulus 
really acts upon the parts to which it is applied; it is 
impossible to conclude that it is conducted to the nerve 
by any channel perhaps more in accordance with the 
neuro-pathological doctrine, and then only by reflex 
action conveyed back again to the parts. 

There certainly are but few tissues in the body which 
are so completely destitute of nerves as cartilage, but 
even when we observe what happens in the parts most 
abundantly supplied with nerves, we find in every case, 
that the extent of the irritation, or to speak more accu- 
rately, the extent of the irritated area, by no means cor- 
responds to the size of any particular nerve-territory, but 
that in a tissue in other respects normal the size of the 
affected area essentially corresponds to that of the local 
irritation. If we make the experiment with the thread, 


upon the skin, a whole series of nerve-territories are 
22 


838 LECTURE XIV. 


intersected by it. Still the whole of the territories be- 
longing to the nerves which lie along the thread, are not 
thrown into the same morbid condition, but the nutritive — 
irritation is limited to the immediate vicinity of the 
thread. No surgeon expects in operations of the kind, 
that all the nerve-territories traversed by the thread, 
will become diseased in their whole extent. Great com- 
plaints would have to be raised against nature, if every 
ligature, every seton were to exercise an irritating influ- 
‘ence, beyond the limits of the parts with which it is in 
immediate contact, upon the whole extent of the nerve- 
districts which it passes through. Thus we see in a tis- 
sue in which what takes place in such a case can be very 
clearly traced, namely in the cornea, that in parts of it 
to which no vessels extend, there are certainly still nerves 
which possess a reticular arrangement, and leave larger 
and smaller districts of tissue between them altogether 
devoid of nerves. Nowif we apply any stimulus directly 
to the cornea, as for example, a red hot needle, or lunar 
caustic, the district which is thereby set in morbid action 
by no means corresponds to the distribution of any nerve. 
It once happened to me with a rabbit that the cautery 
lighted precisely upon a nervous filament, but the mor- 
bid action remained confined to the immediate vicinity 
of this spot, and by no means spread over the whole dis- 
trict appertaining to the nerve. 

It is therefore utterly impossible, even if observations, 
like those on cartilage which I have laid before you, 
are not allowed to have any weight, not to admit that 
the phenomena of irritation in parts supplied with 
nerves are in no respect different from those which 
occur in nerveless parts, and that the immediate effects 
essentially depend upon the enlargement and tumefac- 
tion of the surrounding elements, so that when there are 
many of them, a visible swelling of the whole part is 

















PARENCHYMATOUS KERATITIS. 339 


the result. This is what you observe when a ligature is 
anywhere drawn through the skin. If on the following 
day the immediate vicinity of the thread be examined, 
an active enlargement of the cellular elements is found, 
quite irrespective of the distribution of vessels and 
nerves in the part. 

There is, as you see, an essential difference between 
what I here lay down and the opinions which have gene- 
rally been advanced with regard to the proximate causes 
of these swellings. According to the old maxim: ubi 
stimulus, ibi affluxus, it was generally conceived that 
the first thing which took place was an increased afflux 
of blood (which was itself referred by the neuro-patho- 
logists to the excitation of sensitive nerves), and then 
that the immediate consequence of the increased afflux 
was an increased excretion of fluid from the blood, 
constituting the exudation which filled the part. 

In the first timid attempts which I made to alter this 
conception, I employed the expression parenchymatous* 
exudation, retaining the term exudation, out of deference 
to prevailing opinion. I had, namely, convinced my- 
self that in many places where a swelling had occurred, 
there was absolutely nothing else to be seen than tissue. 
In a tissue which consisted of cells, I could, after the 
swelling (exudation) had taken place, still see nothing 


* The term Parenchyma was first employed by Erasistratus of Alexandria to de- 
signate the mass of tissue which lies between the vessels of a part, and in his opinion 
formed a kind of affusion from them. Thus Galen says (Isagoge s. Introductio, 
cap. xi.): ‘‘ Cerebrum ex nullo principali vase compositum esse videtur Erasistrato, 
eoque nutrimenti parenchyma, ¢. e., affusio, ipsi esse videtur.” In the same way 


, the word is used by Vesalius (De humani corp. fabrica, lib. V., cap. 7) and by 


Thom. Bartholin (Anatome, lib. I., cap. 14), for the proper substance of the liver, 
lying external to, or between, the vessels, It therefore essentially denotes the 
tissue of which an organ is constituted. In a narrower sense those constituents of 
an organ which are peculiar to it, and give it its specific character, may be distin- 
guished as its proper parenchyma, in contra-distinction to its merely interstitial 
tissue. In my book the term has been used in both of these senses.—From a MS. 
Note by the Author 


340 LECTURE XIV. 


but cells; in tissues composed of cells and intercellular 
substance, nothing but cells and intercellular substance ; 
the individual elements indeed were larger, fuller and 
filed with a quantity of matter with which they ought 
not to have been filled, but there was no exudation in 
the manner in which it had been imagined to exist, 
namely free, or in the interstices of the tissue. All the 
matter was contained in the elements of the tissues 
themselves. This was what I intended to express by 
the term, parenchymatous exudation, and hence the 
name, parenchymatous inflammation, is derived—a name 
which was, indeed, used in former times, but in quite 
another sense from that I meant—and which is now 
more generally employed than is perhaps desirable. It 
is, however, at all events important that you should 
draw a distinct line of demarcation between this form 
of irritation as a general standard and the other forms 
(especially the formative one), inasmuch as in it only 
the constituent elements of a tissue already existing 
in the body take up a larger quantity of material, and 
besides these enlarged elements nothing else is present. 

I will immediately send round a preparation to you, 
in which you will see a very characteristic example of . 
such an inflammation. It is almost the most striking 
example which for a long time has come before me. It 
is a specimen from a case of so-called Keratitis, from 
one of Herr von Graefe’s patients, in whom, after vio- 
lent, diffuse phlegmonous inflammation of the extremi- 
ties, an extremely rapid inflammatory opacity of the 
cornea took place. When the cornea was put into my 
hands, it seemed to me as if it were opaque and swollen 
in its whole thickness. The vessels of the borders were 
very full of blood. But when I made a section through 
the part, it at once became evident, even with a low 
power, that the opacity extended by no means uni- 








PARENCHYMATOUS KERATITIS. 341 


formly throughout the whole cornea, but was limited 
to a definite portion of the tissue. This portion is so 
characteristic in reference to the different explanations 
possible, that the case, I think, presents especial inter- 
est theoretically. 

It turned out namely that the opacity began in the 
immediate proximity of the posterior surface and at the 
circumference of the cornea, close to the membrane of 
Descemet [posterior elastic lamina of Bowman] at the 
point where the iris is attached. Thence the opacity, 
assuming almost the shape ofa flight of steps, mounted 
up into the cornea till within a certain distance of the 
external surface. Then it proceeded at the same level, 
till it descended upon the other side again in a similar 


.manner. Thus an opaque bow was formed throughout 


the whole substance of the cornea, without reaching the 
external (anterior) surface and without encroaching 
upon the central parts of the posterior surface. If we 





imagine the nutrition of the cornea to proceed from the 
aqueous humour, the opacity did not assume the form 


Fig. 99. Parenchymatous keratitis. .A, A, Anterior (external), B, B, posterior 
(internal) side of the cornea. ©, 0. The clouded zone with enlarged cornea-cor- 
puscles, 18 diameters. 


349 LECTURE XIV. 


that might have been looked for, for then we should 
rather have expected that the hindermost layer would be 
the first to undergo the change. If any influence from 
without had been here in operation, the opacity must 
have been seated in the most anterior layers ; if again 
the opacity were one which essentially proceeded from the 
vessels, we might, inasmuch as they chiefly lie along the 
border and nearer to the anterior surface, have expected 
to find the principal disease there. Finally, if the 
changes had their origin in the nerves, we should have 
found the opacity spread in the form of a network on 
the surface—and not a bow of this kind. 

The substance of the cornea consists, you know, ac- 
cording to general opinion, of lamelle (plates) which 
run in a more or less parallel direction through the 


Fig. 100. 



































cornea. Now if this opinion be the correct one, we 
should have to deal with a process which, whilst advanc- 


Fig. 100. Perpendicular section of the cornea of the ox, for the purpose of showing 
the form and anastomoses of its cells (corpuscles). Here and there are seen the 
cut ends of some of the processes of the cells, looking like fibres or points. 500 
diameters. From His, ‘Wurzb, Verhandl,’ IV., plate IV., fig. I. 


STRUCTURE OF THE CORNEA. 343 


ing from lamella to lamella, each time moved a little 
farther on. Only the cornea is not composed of perfect 
lamelle, but of layers, which certainly are on the 
whole placed one against the other in a lamellar form, 
but yet are connected with one another ; they do not 
lie any how, more or less firmly or loosely upon one 
another, but there exist direct connections between 
them. It is therefore rather a large coherent mass, 
which is interrupted in certain directions by cellular ele- 
ments, just as is the case in the very different tissues 
which we have already specially considered. A vertical 
section discloses spindle-shaped cells which anastomose 
with one another, but at the same time also possess 
lateral processes; and in consequence of their being 
regularly imbedded in the basis substance, this lamellar, 
foliated or plate-like arrangement of the whole tissue is 
produced. When viewed upon the surface, in horizontal 
section, they show themselves in the form of many-rayed, 
stellate but very flat cells, which may be compared to 
bone-corpuscles. 
Fie. 101. 


\ eumgnti. 


AN CS) 
‘ 
a 


een \Gn 


TWO 





If now in this case of ours we follow the process with 
a higher power, we discover, what may easily be shown 


Fig. 101. Horizontal section of the cornea, parallel to the surface and showing 
the stellate, flat corpuscles, with their anastomosing processes. From His, loc. cit., 
fig. II. 


344 LECTURE XIV. 


to be the case in every form of keratitis, that the change 
is essentially seated in the corpuscles or cells of the cor- 
nea, and that in proportion as we approach the clouded 
spot either from without or within, the little narrow cells 
continually become larger and more cloudy. At last we 
find them presenting almost the appearance of sacculated 
canals or tubes. Whilst this enlargement of the elements, 
this acute hypertrophy, if you will, is going on, the con- 
tents of the cells are at the same time becoming more 
cloudy, and it is this cloudiness of the contents which in 
its turn occasions the opacity of the whole coat, for the 
proper basis-substance appears to be altogether unaf- 


Fig. 102. 





fected. This cloudiness of the contents is in part occa- 
sioned by particles which are of a fatty nature, so that 
the process seems to have begun to assume the character 
of a degenerative disease. I should have had no hesita- 
tion in believing that a destruction of the cornea had here 

Fig. 102. Parenchymatous keratitis (cf. Fig. 99), seen with a higher power. At 


A the cornea-corpuscles in a nearly normal condition, at B enlarged, at Cand /D 
still more enlarged, and at the same time clouded, 350 diameters. 


NUTRITIVE AND FORMATIVE IRRITATION. 845 


really set in, but Herr v. Graefe assures me that, from 
what he has seen, such conditions may, when the disease 
runs a favourable course, terminate in resolution, And 
there is really nothing at all in the matter at variance 
with this possibility ; for, since the cells still exist and 
the only thing required is that their changed contents 
be get rid of, a complete restitution may no doubt take 
place. 

Now just this doctrine of a s¢tmply nutritive restitutional 
power is of very great importance practically. In such a 
case as this, where nothing has taken place excepting 
that the cells, without ceasing to display their activity, 
have accumulated in their cavities a larger quantity of 
material than usual, everything is prepared for the pro- 
cess which we call reabsorption ; the cells can transform 
a certain quantity of the material and convert it into 
soluble substances, and the material in this form may dis- 
appear in the very same way in which it came. The 
structure in the main remains the same all the while 
nothing foreign has thrust itself in between the parts 
the tissue presents throughout its original constituents. 

From the phenomena of this nutritive irritation direct 
transitions to incipient formative changes are often seen. 
If namely, we follow up the higher degrees of irritation 
which take place in a part, we find that the cellular ele? 
ments, shortly after they have experienced the nutritive 
enlargement, exhibit further changes which begin in the 
interior of the nuclei, generally in such a manner that the 
nucleoli become unusually large, in many cases some- 
what oblong, and sometimes staff-shaped. Then as the 
next stage we usually see that the nucleoli become con- 
stricted in the middle, and assume the form of a finger- 
biscuit (Bisquit), and a little later two nucleoli are found. 
This division of the nucleoli is an indication of the impend- 
ing division of the nucleus itself, and the next stage is, 


346 | LECTURE XIV. 


that about such a divided nucleolus the finger-biscuit-like 
constriction, and afterwards the real division, of the nu- 


Fie. 103. 





cleus takes place, as we have already seen in colourless 
blood- and pus-corpuscles (Figs. 11, A, 6; 56, 63). Here 
we manifestly have to deal with something essentially 
different from what we had before. In the simple hy- 
pertrophy consequent upon nutritive irritation, the nu- 
cleus may remain quite intact ; here, on the other hand, 
we frequently see that the contents display a relatively 
slight amount of change, the utmost being that the cells 
become larger, whence we infer that a quantity of new 
material has been taken up into them. 

In many cases the changes are limited to this series of 
transformations, of which the division of the nucleus must 
be regarded as the conclusion. This may be repeated, 
so that three, four or more nuclei arise (Fig. 15, 0, c, d). 
Thus it comes to pass that we sometimes find cells—not 
merely in pathological conditions, but also not unfre- 
quently where the development is altogether normal 
which contain twenty to thirty nuclei or more. Recently 
in the marrow of bones, especially in young children, 
cells have been observed, where the entire structure is 





Fig. 1038. Cells from a melanotic tumour of the parotid gland extirpated in 1851 
by Herr Textor. A. Free cells with division of the nucleoliand nuclei. B. Net- 
work of connective tissue-corpuscles with division of their nuclei. 300 diameters. 


DIVISION OF NUCLEOLI. 847 


full of nuclei, which often attain the size of the whole 
original cell. Such formations occur in many tumours in 


Fig. 104. 





such large quantities, that in England a particular species 
is thereby distinguished, and on the proposal of Paget a 
myeloid tumour (medullary swelling) has been received 
into the classification. This formation is not, however, 
confined to the medulla of the bones, but occasionally 
occurs in nearly all situations. 

Muscle, upon irritation, exhibits precisely similar forms, 
Whilst transversely striated muscles are generally pro- 
vided with nuclei at certain intervals, though in no great 
abundance, we find, on examining a muscle in the neigh- 
bourhood of an irritated part, as for example, a wound, 
a corroded or ulcerated surface, that a multiplication of 
the nuclei is going on in it; we see nuclei with two nu- 
cleoli; then come constricted, and then divided, nuclei 
(Comp. Figs. 23, 6, c; 24,.B,C’), and so it goes on, until 
we find in different places whole groups of nuclei lying 
side by side, in which the divisions have taken place to a 
large extent, or else whole rows of them, one behind the 
other. In the most marked cases of this sort the num- 
ber of nuclei increases to such a degree, that at first sight 
we can scarcely believe we are looking at muscles; and 
that fragments of the primitive fasciculi offer the greatest 

Fig. 104. Cells from the marrow of bones. a. Small cells with single and divided 


nuclei. 6, 6. Large, many-nucleated cells. 350 diameters, From Kolliker, ‘ Mikr. 
Anat.,’ I., p. 364, fig. 113. 


348 LECTURE XIV. 


resemblance to those plaques a plusieurs noyaux which 
Robin has described in the marrow of bones. This is 
something quite peculiar which looks extremely like the 
commencement of a real new- 
formation, only that new-forma- 
tions in the ordinary sense of 
the word are not limited to sin- 
gle cell-constituents. Besides 
we must bear in mind this very 
important fact, that exactly the 
same limitation takes place in the 
earliest embryonic development 
of muscle, in the course of the 
first growth of the primitive 
muscular fasciculi. For this is 
the manner in which muscle 
originally grows. Ifa growing 
muscle be watched, the same 
division of the nuclei is wit- 
nessed, and after groups and 
rows of nuclei have arisen in it, they are, in the course 
of growth, gradually thrust farther and farther asunder 
by the continual increase of the intermediate sarcous sub- 
stance. Nowalthough a growth in length has not as yet 
been demonstrated with certainty in a pathologically irri- 
tated muscle—I say demonstrated, because there really 
is a probability that something of the kind may yet be 
proved to be the case—we must still hold the perfect 
analogy of morbid irritative processes with the natural 
ones of growth to be a well-ascertained fact. For the 
formative act of real growth begins with a multiplication 


Fig. 105. 





Fig. 105. Division of nuclei in primitive muscular fasciculi from the immediate 
neighbourhood of a cancerous tumour in the thigh. At A a primitive fasciculus, 
the transverse striation of which is not represented all the way down, with its na- 
tural, spindle-shaped extremity f, and incipient multiplication of the nuclei. 2B. 
Strongly marked proliferation of nuclei. 300 diameters, 


NEW FORMATION OF CELLS. 849 


of the centres, inasmuch as the nuclei must, as was long 
since shown by John Goodsir, be regarded as the central 
organs of the cells. 

If now, gentlemen, we advance a step further in these 
processes, we come to the new formation of the cells them-— 
selves. After the multiplication of the nuclei has taken 
place, the cell may certainly, as we have seen, continue to 
subsist as a coherent structure ; still the rule is, that even 
after the first division of the nuclei, the cells themselves 
undergo division, and that after some time two cells are 
found lying closely side by side, separated by a more or 
less straight partition, and each provided with a nucleus 
of its own (Fig. 6, 6, 6). This is the natural, regular 
manner in which the real multiplication of cellular ele- 
ments takes place. Then, the two cells may separate, if 
the tissue is one which possesses intercellular substance 
(Fig. 6, c, d) ; or may remain lying close to one another, 
in the case of a tissue simply composed of cells (Fig. 27, 
C). This series of processes, which in their subsequent 
course lead to a continually proceeding division of the 


Fig. 106. 





cells, and to the production of large groups of cells from 
single ones (Figs. 9, 22), occurs in the adult body just as 
unquestionably as the result of a direct irritation of the 
tissues, as the class we spoke of before. If, for example, 
we follow up a little farther the case which we before 
considered, of the production of a simple mechanical 
irritation by drawing a thread through the parts, we usu- 


Fig. 106. Cells from the central substance of an intervertebral cartilage of an 
adult. Intra-capsular multiplication of cells, 300 diameters. 


350 LECTURE XIV. 


ally observe that the swelling is not simply limited to 
the enlargement of the existing cells, but that they divide 
and multiply. Round about a thread, which we draw 
through the skin, a number of young cells generally show 
themselves as early as the second day. The same change 
may be brought about by the application of a chemical 
stimulus. If, for example, caustics be applied to the sur- 
face of a part, the first thing that happens is that the 
cells swell up and then, when the process follows a regu- 
lar course, divide, and begin to proliferate more or less 
abundantly. Here too we have still to deal with actions 
which do not exhibit the slightest difference in the real 
mode of their accomplishment, whether the part be pro- 
vided with nefves, or destitute of them, whether it con- 
tain vessels or not. 
Accordingly, we cannot say that any part of these - 
processes appears to be necessarily dependent upon ner- 
vous or vascular influence, but, on the contrary, we are 
in all these cases referred to the parts themselves. The 
relation of the vessels is not by any means to be ex- 
plained in the way in which it is ordinarily done; the 
absorption of matter into the interior of the cells is un- 
questionably an act of the cells themselves, for we are 
as yet acquainted with no method enabling us to pro- 
duce this kind of proliferation in the body, by any mode 
of experimentation, through the medium of an agency 
primarily affecting either the nerves or the vessels. The 
circulation may be heightened in the parts as far as it is 
possible to heighten it, without the production of such 
an increased nutrition of the parts as to give rise to any 
swelling or multiplication of the elements themselves. 
Those very experiments too upon the section of the 
sympathetic nerve which I have already mentioned, 
have, as is well known, proved (I myself have very fre- 
quently performed this experiment and watched its 


ha Siey 
Cs 
a 


NEURO-PARALYTICAL INFLAMMATION. 351 


effects with this especial object) that an increased 
afflux of blood may last for weeks—an afflux of blood 
accompanied by a marked elevation of temperature and 
corresponding redness, as great, both of them, as we 
ever meet with in. inflammations—without the produc- 
tion of the least enlargement in the cells of the part, or 
the excitation of any process of proliferation in them. 
Irritation of the nerves may be combined therewith. 
But when the tissues themselves are not irritated, when 
the irritation is not made to act upon the parts them- 
selves, either by the direct application of the irritating 
matters, or by their introduction into the blood, the 
occurrence of these changes cannot be relied upon. 
This is a most important argument, from which I draw 
the conclusion that these active processes have their 
foundation in the special action of the elementary parts, 
an action which does not depend upon an increased 
afflux of blood or any excitation of the nerves, but 
which is certainly promoted by them, though it can also 
continue entirely independent of them, and manifests 
itself with just as great distinctness in a paralyzed and 
nerveless part. 

In support of these positions I will only add that 
more recent observations have gradually done away 
with the whole class of the so-called newro-paralytical 
inflammations. The two nerves with which we are 
almost exclusively concerned in the discussion of inflam- 
matory phenomena, are the pneumogastric and the fifth 
pair, after the section of which, in one case, pneumonia, 
in the other, those celebrated changes in the eyeball 
have been observed to declare themselves. These ob- 
servations have now been explained in this way, that 
inflammations certainly may come on after such sections, 
but that the real interpretation to be put upon them is, 


352 LECTURE XIV. 


that they manifest themselves in spite of the section.® 
With regard to the pneumogastric it was, as is well 
known, long since shown by Traube that the paralysis 
of the rima glottidis, whereby the entrance of the buc- 
cal fluids into the air-passages is facilitated, is the 
principal source of the inflammation ; besides, the more 
accurate interpretation of the pathological specimens 
has determined, that a great part of what had been 
called pneumonia, was really nothing more than atelec- 
tasis with hyperemia of the lungs; actual pneumonia 
may with certainty be avoided, if the possibility of the 
penetration of foreign bodies into the bronchi is cut off. 
The same has been ascertained to be the case with the 
inflammations coming on after the section of the fifth 
pair, and indeed by means of a very simple experiment. 
After a number of attempts of the most varied kind 
had been made for the purpose of removing the different 
disturbing influences affecting the eye that was deprived 
of its sensibility, a very simple method was at last dis- 
covered in Utrecht for providing the eye with a substi- 
tute for its sensitive apparatus; for Snellen sewed be- 
fore the eyes of animals, in which he had cut the fifth 
pair, their still sensitive ears. From that time the ani- 
mals had no more attacks of inflammation, inasmuch as 
on the one hand a direct protection was afforded to the 
eye, and on the other the animals were preserved by 
the presence of a sensitive covering from all traumatic 
influences. As soon as sensation was re-established, not 
in the eye itself, but only before the eye, what was 
really nothing more than a traumatic inflammation was 
got rid of.+ 


* For if, as the neuro-pathologists assume, irritation produces inflammation 
through the medium of the nerves, then, when the nerves are cut, all inflammation 
ought to be impossible. 


t In the text the influence of the section of nerves is perhaps not described with 


NEURO-PARALYTICAL INFLAMMATION. 353 


We can therefore now say, there is no form of dis- 
turbance of this kind known which can be traced to the 
abolition of the action of a nerve. A part may be para- 
lyzed without becoming inflamed ; it may be anesthetic 
without becoming exposed to this danger. There is 
always required in addition some special irritation, either 
of a mechanical or chemical nature, and proceeding 
either from without or from the blood, in order to pro- 
duce the peculiar liability. 


In this manner therefore we have, as you see, a series 
of connecting links between facts eminently pathological 
and the most common processes of physiological life, 
facts of which the special import can, however, only be 
understood and defined, when the distinctions are made 
to which I called your attention at the commencement 
of the lecture, that is, when the different kinds of irrita- 
tion are separated according to their functional, nutritive 


sufficient minuteness. According to the author’s views, of which a more detailed 
account may be found in his Handbuch der spec. Pathologie und Ther, Erlangen, 
1854 (Vol. I., pp. 31, 50, 80, 276, 314, 319), the section and paralysis of nerves 
certainly exercise some influence upon the nutrition of the tissues, although per- 
haps only an indirect-one. The states arising from such causes he has classed 
together under the name of Neurotic Atrophy. Parts which have in this way 
suffered derangement in their nutrition, and as a consequence have become weak- 


* ened, are less capable of controlling the disorders by which they are attacked, and 


accordingly simple irritation in them readily becomes aggravated into inflammation 
(asthenic inflammation). But in these cases the inflammation is always the conse- 
quence of some special irritation, never the direct result of the section of the 
nerves, Still, as in the case of the fifth pair and the pneumogastric, such section 
may be the cause of irritants’ (foreign bodies and other agents) more readily acting 
upon the anesthetic or paralyzed parts. Cl. Bernard has recently declared that the 
section or irritation of nerves in weakened parts produces effects which cannot be 
elicited in healthy ones. We have therefore here to deal with a very complicated 
state of things. The change in the nerve is generally succeeded by a disturbance 
in the function or circulation of the part, or in both, and when the part is already 
weakened (7. ¢., altered in its nutrition) this disturbance may prove a source of 
irritation to it, and thus the effects be produced which Bernard ascribes to other 
causes. In quite a similar manner we see that, even when the nervous supply is in 
its normal state, purely mechanical disturbances in the circulation act “apon weak- 
ened parts as morbid irritants —From a MS. Note by the Author. 
23 


3h4 LECTURE XIV. 


or formative nature. If they are jumbled together, as 
they have been by the neurists, and especially, if the 
formative and nutritive processes are not kept apart, 
then it is impossible to arrive at any simple explanation 
of the phenomena. 

Those states of irritation which we witness in the 
course of the severer forms of disease—the really 
inflammatory kinds of wrritation—never in any case 
admit of a simple explanation. In inflammation we 
find side by side all the forms of irritation of which I 
have given you an analysis. Indeed, we very frequently 
see, that when the organ itself is made up of different 
parts, one part of the tissue undergoes functional or 
nutritive, another formative changes. If we consider 
what happens in a muscle, a chemical or traumatic 
stimulus will perhaps in the first instance produce a 
functional irritation of the primitive fasciculi ; the mus- 
cle contracts, but then nutritive disturbances declare 
themselves. On the other hand in the interstitial con- 
nective tissue, which binds the individual fasciculi of the 
muscle together, real new-formations are readily pro- 
duced, commonly pus. Here we have to deal with a 
formative irritation, whilst the inflamed primitive fasci- 
culus commonly produces no pus, any more than it does 
new muscular substance ; on the contrary we most fre- 
quently see, when the irritation has attained a certain 
height, degenerative processes set in. In this manner 
the three forms of irritation may be distinguished in one 
part. Of course there may be in addition also an irri- 
tation of the nerves, but this has, at least if we do 
not take function into account, no. connection of cause 
and effect with the processes going on in the tissue 
proper, but is nothing more than a collateral effect of 
the oniginal disturbance. This must, in my opinion, 
be regarded as the most important result derived from 


INFLAMMATORY IRRITATION. 355 


the facts of Special Histology, and it is all the more 
certain because it can be tested both by experiment and 
by physiological and pathological experience. 

Soon, I will show you how in the study of inflamma- 
tory processes a clearer apprehension of their nature 
may hereby be obtained. 


hea Wri ase Vv 
| APRIL 10, 1858. 


PASSIVE PROCESSES. FATTY DEGENERATION. 


Passive processes in their two chief tendencies to degeneration; Necrobiosis (soft 
ening and disintegration) and induration. 

Fatty degeneration—Histological history of fat in the animal body; fat as a com- 
ponent of the tissues, as a transitory infiltration, and as a necrobiotic matter. 

Adipose tissue—Polysarcia—Fatty tumours—Interstitial formation of fat—Fatty 
degeneration of muscles. 

Fatty infiltration—Intestines ; structure and functions of the villi—Reabsorption 
and retention of the chyle—Liver; intermediate interchange of matter by 
means of the biliary ducts. Fatty liver. 

Fatty metamorphosis—Glands; secretion of sebaceous matter and milk (colostrum) 
—Granule-cells and granule-globules—Inflammatory globules—Arteries; fatty 
usure and atheroma in them—Fatty débris. 


WE have, gentlemen, hitherto nearly always spoken 
of the actions of cells and the processes which manifest 
themselves in them, when, in consequence of any exter- 
nal influence, they give signs of their vitality. There 
take place in the body, however, also a tolerably large 
number of passive processes, in which, as far at least as 
can be demonstrated, there is no particular activity dis- 
played by the cells. Allow me ,therefore, before we 
proceed farther in the description of the active processes, 
to speak a little more in detail concerning these passive 


processes. For the history of the affections of cells, as. 


they are exhibited to us in our patients, is generally 
856 








DEGENERATION. 357 


composed of processes, which belong, some of them, 
rather to the active class, and some of them, rather to 
the passive one; and the obvious results are in many | 
cases apparently so similar in both classes, that the ulti- 
mate changes which we meet with, after the continuance 
of the process for a certain time, may very nearly be 
the same. Here particularly it was for a time, very 
difficult to define the boundaries, and a great part 
of the confusion which marked early. microscopical 
efforts, was. occasioned by the extraordinary difficulty 
there was in separating active and passive disturbances. 

Passive disturbances I call those changes in cellular 
elements, whereby they at once either merely lose a por- 
tion of their activity, or are so completely destroyed, that 
a loss of substance, a diminution in the sum total of the 
constituents of the body is produced. Both series of pas- 
sive processes, taken together, viz., those which are in the 
first instance marked by an essential diminution of power, 
and those which terminate in a complete destruction of 
the parts, constitute the chief part of the domain of what 
is called degeneration, although—a point that we must 
hereafter consider more closely—a great part of what 
must be called degeneration must be transferred to the 
series of active processes. 

It makes of course an extremely great difference whe-: 
ther a vital element continues to subsist as such, or whe- 
ther it entirely and completely perishes: whether at the 
conclusion of the process, it still exists, even though in a 
condition of much diminished functional power, or whe- 
ther it is altogether destroyed. And here we have the 
important practical distinction, that in the one series of 
processes there is a possibility of a repair of the cells, 
whilst in the other direct repair is impossible, and a rege- 
neration can only take place by means of a substitution 
of new cells from the neighbourhood. For when a cell 


358 LECTURE XV. 


has perished, it is of course impossible for any further 
development to originate in it. 

This latter category, where the cells are destroyed 
during the course of the process, I proposed a few years 
ago to designate by a term which has been employed to: 
express disease generally by K. H. Schultz, viz., Necro- 
biosis.* For we have, namely, always here to deal with 
a gradual decay and death, a dissolution, we might almost _ 
say, a necrosis. But the idea of necrosis really does not 
offer any analogy to these processes, inasmnch as in ne- ~ 
crosis we conceive the mortified part to be preserved 
more or less in its external form. Here on the contrary 
the part vanishes, so that we can no longer perceive it 
in its previous form. We have no necrosed fragment at 
the end of the process, no mortification of the ordinary 
kind, but a mass in which absolutely nothing of the pre- 
viously existing tissues is preserved. The necrobiotic pro- 
cesses, which must be completely separated from necrosis, 
are in general attended by softening as their ultimate re- 
sult. This commences with a friability of the parts ; they 
lose their coherence, at last really liquefy, and more or less 
moveable, pulpy or fluid products take their place. We 
might therefore without more ado name this whole series 
of necrobiotic processes softenings, if a number of them 
did not run their course, without the malacia’s ever be- 
coming apparent to the naked eye. As soon, namely, 
as a process of this sort sets in in a compound organ, as 
for example, a muscle, a palpable myo-malacia is cer- 
tainly produced when all the muscular elements at a 
given point are at once affected ; but it happens far more. 
“requently that, in the course of a muscle, only a compa- 
ratively small number of primitive fasciculi are affected; 


* Necrobiosis is death brought on by (altered) /éfe—a spontaneous wearing out 
of living parts—the destruction and annihilation consequent upon life—natural as 
opposed to violent death (mortification.) —From a MS. Note by the Author. 





FATTY DEGENERATION. a 359 


whilst the others remain almost intact. Then indeed a 
softening really does occur, but such a minute one, that 
it is altogether imperceptible to the naked eye and can 
only be demonstrated microscopically. In this case we 
generally make use of the expression, atrophy of muscle, 
although the process which has attacked the individual 
primitive fasciculi, does not in any way differ in its na- 
ture from the processes which we, at other times term 
softening of muscle. 

This is the reason, why the term softening, which must 
be reserved for coarse pathological anatomy, cannot sim- 
ply be. applied to histological processes, and. why it is 
better to say necrobiosis, when we have to do with these 
more delicate processes. The common feature of all the 
varieties of the necrobiotic process is, you know, that the 
affected part at the close of the process is destroyed, nay 
annihilated. , 

A second class of passive processes is formed by the 
simply degenerative forms, in which, at the conclusion of 
the process, the affected part is in some condition or other 
less fitting it for action, and has generally become more 
rigid. This group might therefore be termed hardenings 
(indurations) and thus a group be formed distinguishable 
even externally from the necrobiotic processes. Only 
the term induration also would easily be misunderstood, 
inasmuch as in this class likewise many conditions occur, 
in which the hardness of the organ on the whole at least 
does not become more considerable, but only isolated, 
very minute parts undergo change, so that no very strik- 
ing effects are apparent to the sense of touch. 

Allow me now to hold up to you as types a few of the 
processes belonging to this class, which are of the great- 
est importance in a directly practical point of view. 


Among the necrobiotic processes the one which is un- 


360 LECTURE XV. 


questionably the most widely spread and the most im- 
portant in the course of all cellular disturbances, is fatty 
metamorphosis, or as it has also longabeen wont to be 
called, fatty degeneration. This process is attended by a 
continually increasing accumulation of fat in different | 
organs. Even the old notion of fatty degeneration in- 
volved the idea of a continually increasing change of such 
a nature that pure fat at last took the place of whole 
parts of organs. It has turned out, however, that this 
old notion, which is even now retained by many in the 
language of pathology, includes a great number of com- 
pletely different processes, and that errors would inevit- 
ably be committed if it were sought to interpret the whole 
group from a pathogenical point of view, in a simple 
manner. 

The history of fat in its relation to the tissues may, gene- 
rally speaking, be considered under three aspects. We 
find namely one class of tissues in the body, which serve 
as physiological reservoirs for fat, and in which the fat is 
contained as a kind of necessary appurtenance, without 
however their own permanency being in any way en- 
dangered by its presence. On the contrary, we are actu- 
ally accustomed to estimate the well-being of an indivi- 
dual by the amount of fat contained in certain tissues, 
and to regard the degree of fulness presented by the in- 
dividual fat-cells as a criterion of the successful progress 
of the interchange of matter generally. This forms there- 
fore a complete contrast to the necrobiotic processes, in 
which the part, in consequence of the accumulation of fat, 
really altogether ceases to exist. 

A second series of tissues do not constitute regular re- 
servoirs for fat, on the contrary fat is found in them only 
_ at certain times and transitorily, for after a short time it 
again disappears from them, without their being on that 
account left in an altered state. This is the case in the 


PHYSIOLOGICAL FATTY METAMORPHOSIS. 861 


ordinary absorption of fat from the intestinal canal. 
When we drink milk, we expect in accordance with old 
experience that itgvill gradually pass from the intestines 
into the lacteals, and thence be conveyed into the blood ; 
we know that the passage of digested matters from the 
intestines into the lacteals takes place through the epithe- 
lium and the villi, and that some hours after a meal the 
epithelium and the villiare full of fat. Now, with respect 
to such a fat-containing villus or epithelial cell, we take 
for granted that in the natural course of events it will at 
last yield up its fat, and after. some time again become 
perfectly free from it. This is fatty infiltration of a 
purely. transitory character. _ 

Finally, we have a, third series of processes, namely, 
those which lead to necrobiosis and which have of late 
frequently been regarded as peculiarly pathological ones. 
But, as it has been shown to be the case in all other con- 
ditions that pathological processes are not specific ones, 
but, on the contrary, that others analogous to them exist 
in normal life, so also the conviction has been acquired 
that this necrobiotic development of fat is an entirely 
regular and typical process in certain parts of the body, 
nay that it is even met. with in very obvious forms in 
physiological life. The most important types of this pro- 
cess we find on the one hand in the secretion of milk, 
the sebaceous matter of the skin, the cerumen of the ears, 
etc., and on the other in the formation of the corpus lu- 
teum in the ovaries. In all these parts a development 
of fat takes place precisely in the same manner that we 
meet with it in the nocrobiotice fatty metamorphosis 
occurring from morbid causes, and in what we call seba- 
ceous matter, milk or colostrum we have formations ana- 
logous to the pathological masses of fat which constitute | 
fatty softening. If in any person milk is manufactured 
in the brain instead of in the mammary gland, this con- 


362 LECTURE XV. 


stitutes one form of cerebral softening ; the product may 
morphologically exactly correspond with what in the 
mammary gland would have been quite normal. The great 
difference, however, is this, that, whilst in the mammary 
gland the cells which perish are replaced by a succession 
of new cells, the disintegration of elements in an organ 
which is not arranged so as to furnish such a succession, 
leads to a permanent loss of substance. The same process 
which in one organ yields the happiest, nay the sweetest, 
results, brings along with it in another, painful lesions. 
If then you picture to yourselves these three different 
physiological types, we have in the first case an accumu- 
lation of fat in the cells in such a way, that at the close 
of the process every single cell is entirely full of it. This 
yields us the type of the so-called adipose cellular tissue, 
or simply, adzpose tissue, as it occurs in such large masses 
especially in the subcutaneous tissue, where it on the 
one hand gives rise to beauty, particularly in the female 
figure, and on the other to the pathological conditions of 
obesity or polysarcia. Fat-cells always possess a mem- 
brane and fatty contents, but the fat so completely fills 
up the interior, and the membrane is so extremely thin, 
delicate and tense, that usually nothing else is seen than 


Hid, 107; 





Fig. 107. Adipose cellular tissue from the panniculus [adiposus.] A. Ordinary 
subcutaneous tissue, with fat-cells, some interstitial tissue, and at 5 vascular loops ; 
a, an isolated fat-cell with membrane, nucleus and nucleolus. B. Atrophic fat in 
phthisis. 300 diameters. 


* 


ADIPOSE TISSUE—FATTY DEGENERATION OF MUSCLES. 363 


the drop of fat, and thus it was, until very recently, still 
a matter of discussion whether the fat-cells really were 
cells. Itis in reality very difficult to come to a. distinct 
decision upon the subject, but supporting testimony of a 
very beautiful character is supplied in the course of natu- 
ral processes. When a person becomes thinner, the fat 
gradually disappears, the membrane loses somewhat of 
its tension, is no longer so thin and delicate, and thus 
becomes more clearly manifest, being sometimes distinctly 
separated from the drop of fat, and even provided with.a 
recognizable nucleus (Fig. 107, A, a). We have here 
therefore a real, complete cell with nucleus and mem- 
brane, though the contents have been almost entirely sup- 
planted by the fat it has taken up. This so-called adi- 
pose cellular tissue is a form of connective tissue (p. 76), 
and when it undergoes retrogressive metamorphosis, it is 
clearly seen to be reduced to connective or mucous tis- 
sue, for between the cells a small quantity of intercellu- 
lar substance again becomes apparent (Fig. 107, A, 5, B). 

This species of adipose tissue it is, gentlemen, which 
under certain circumstances not only gives rise to poly- 
sarcia and obesity, from continually increasing quantities 
of connective tissue becoming involved in this accumu- 
lation of fat, but is also the foundation of all anomalous 
fatty structures, for example, of lipomata. The differ- 
ent forms of these structures, and particularly real fatty 

tumours, are distinguished from one another only by 
the greater or less quantity of interstitial connective 
tissue, which the tumour contains, and upon which their 
greater or less consistence depends. It is the same 
form of accumulation of fat which we see appear in 
morbid conditions in a series of cases which, in compli- 
ance with old tradition, are still called fatty degenera- 
tion ; and itis indeed particularly the fatty degeneration 
of muscles which in many instances presents nothing 


364 LECTURE XV. 


else than a more or less advanced development of adi- 
pose cellular tissue between the primitive muscular 
fasciculi. It is a similar process to that which we meet 
with in the fattening of animals, and which is often 
exhibited in simply fattened muscles in the human body. 
Fat-cells insinuate themselves between the primitive 
muscular fasciculi, and le of course in stripes in the 
direction of the muscular fibres, which may remain 
unchanged. The development in this case has its origin 
in the interstitial tissue of the muscle. At the com- 
mencement of the development, 
and when it proceeds with very 
great regularity, it may happen, 
that single rows of fat-cells 
lying one behind the other al- 
ternate with the rows of muscu- 
lar elements. In this case, 
where the primitive fasciculi are 
forced asunder, and the circu- 
lation in the muscle is generally 
disturbed in consequence of the abundant development 
of fat, so that the flesh becomes pale—it looks to the 
naked eye as if there no longer existed any muscular 
tissue whatever. If, for example, in an inferior ex- 
tremity, which in consequence of an anchylosis of the 
knee has remained unexercised, the gastrocnemii are 
examined, we find nothing but a yellowish mass exhi- 
biting scarcely any striz and without any appearance 
of flesh, but upon a more minute examination it is dis- 
covered, that the primitive muscular fasciculi still pass, 
essentially unaltered, through the fat. In this case the 
fat forms an impediment to the use of the muscle, but 
the primitive fasciculi still exist and are to a certain 


Fie. 108. 





Fig. 108. Interstitial growth of fat in muscle (fattening). //. Rows of intersti- 
tial fat-cells; m, m, m, primitive muscular fasciculi. $00 diameters. 


TRANSITORY FATTY INFILTRATION, 365 


extent capable of action. This process therefore is 
essentially different from necrobiosis, where the muscu- 
lar fibres as such completely perish. Here we have a 
purely interstitial formation of adipose tissue, ordinary 
connective tissue becoming converted into adipose tissue, 
and the term, fatty degeneration, which is so very liable 
to be misunderstood, should be avoided. 

This form occurs pretty frequently, especially in the 
heart, and may, when it attains a great extent, produce 
considerable derangement in the motor power of the 
muscular substance of this organ, but in pathological 
importance it stands far below real fatty metamorphosis, 
although this again in its outwardly visible results much 
resembles it. The hearts described by the old anato- 
mists as fatty were in a great measure only hearts infil- 
trated with fat; on the other hand, what is meant at 
the present day when genuine fatty degeneration (meta- 
morphosis) of the heart is spoken of, is not this obesity 
of the heart, this interlarding of its fibres with fat-cells, 
but rather a real transformation of its substance, going 
on in the interior of the fibres (Fig. 23). In the latter 
case the fat lies am, in the former between the primitive 
fascicull. , 

The second series of processes consists in the transi- 
tory accumulation of fat in certain organs, as we meet 
with it in a typical form in digestion. When a fatty 
substance has been eaten, and has passed into the state 
of emulsion, we find that, when it has reached the 
upper end of the jejunum, and to some extent even in 
the duodenum, the villi of the mucous membrane be- 
come whitish, clouded and thick, and more minute 
examination shows, that they are filled with extremely 
minute granules, much more minute than can be pro- 
duced by any artificial emulsion. These granules, 
which are found even in the chyme, come in the first 


366 LECTURE XV. 


instance into contact with the cylindrical epithelium 
with which every single intestinal villus is invested. On 
the surface of every epithelial cell we find, as was first 
discovered by KOlliker, a peculiar border which, when 
the cell is seen in profile, exhibits minute and fine striee ; 
when viewed from above, and seen upon the surface, 
the cell appears hexagonal and, as it were, dotted over 
with a number of minute points (Comp. the epithelium 
of the gall-bladder, Fig. 14, and also Fig. 109, A). 
Kélliker has put forward the conjecture, that these fine 
stris and dots correspond to minute pore-canals, and 
that the absorption of the fat is effected by its minute 
particles being taken up through these minute pores 
upon the surface of the epithelial cells. But the object 
is one which is accessible only to the highest powers of 
our optical instruments, and it has therefore hitherto 
been impossible to obtain perfectly clear notions as to 
whether the striz really correspond to fine canals. or 


Fig. 109. 





Fig. 109. Intestinal villi, showing the absorption of fat. .A. Normal human 
intestinal villus from the jejunum; at a@ the cylindrical epithelium in part still 
investing it with the delicate border and nuclei; c, the central lacteal vessel ; 
v, v, blood-vessels ; in the rest of the parenchyma the nuclei of the connective and 
muscular tissue. B. Villus in a state of contraction, from a.dog. C. Human 
intestinal villus during the absorption of chyle, D, in a case of retention of chyle ; 
at the apex a large fat-drop, emerging from a crystalline envelope. 280 diameters, 


ABSORPTION OF FAT IN THE INTESTINES. 367 


whether, as Briicke supposes, the truth is rather that 
the whole of this upper border is composed of little 
rods or pillars resembling cilia. . I must confess that my 
own investigations also have rather disposed me to 
‘adopt this latter opinion, especially as comparative his- 
tology shows us real ciliated epithelium to be the equi- 
valent structure in the same parts. At all events this 
much is certain, that, a short time after digestion has taken 
place, the fat no longer lies only outside, but is found 
also inside, the cells, and first at their outer end; then 
it gradually advances farther and farther inwards in the 
cells, and indeed so distinctly in rows, that it might 
easily give rise to the impression, that fine canals ran 
throughout the whole length of the cells themselves 
(Fig. 109, C, a). But this too is a question which will 
not, [ think, with our present optical instruments, be so 
very speedily settled. At any rate, the plain fact re- 
mains, that the fat passes through the cells, and this 
indeed in such a way, that at first only their outer end 
is filled with it, then a time comes when they are quite 
full of fat, then a little later the outer part again be- 
comes entirely free from it, whilst the inner still con- 
tains a little, until at last all the fat entirely vanishes 
from the cells. In this manner its gradual progress may 
be followed from hour to hour. After the fat has ad- 
vanced as far as the inner extremity of the cells, it 
begins to pass into the so-called parenchyma of the 
villus (Fig. 109, C’). Whether the epithelial cells have 
an orifice below, and whether, as has been quite re- 
cently maintained by Heidenhain junior, they are con- 
nected with extremely minute canals formed by the con- 
nective-tissue-corpuscles, is not quite decided, though it 
is very probable. It is extremely difficult to come to 
any definite conclusions with regard to these extremely 
minute arrangements of the substance of tissues. In 


368 LECTURE XV. 


the interior of the villi we generally find the network 
of blood-vessels a little below the surface (Fig. 109, 
A, v, v), whilst in its axis there is a tolerably wide cana- 
licular cavity with a blunt extremity, the commence- 
ment of the lacteal vessel, as far as it can at present be - 
determined with certainty (Fig. 109, A, c). At the 
periphery of the villi Brticke has discovered a layer of 
muscular fibres, which is of great importance in diges- 
tion, inasmuch as by its help an approximation of the 
apex of the villus to its base, a shortening is effected, 
as may very readily be seen. Upon cutting off villi 
from the intestine of an animal just killed, they 
may be seen under the microscope to contract, become 
wrinkled, thicker and shorter (Fig. 109, B); thereby a 
pressure from without inwards is manifestly produced, 
which promotes the onward movement of the juices. 
So far the matter is tolerably clear, only what sort of 
a structure the rest of the parenchyma has, it is ex- 
tremely difficult to see. Upon the outer side of the 
muscular layer, smallish nuclei are seen, which, as I 
pointed out many years ago, are now and then pretty 
distinctly enclosed in fine, cellular elements. But 
whether these parenchymatous cells anastomose with 
one another so as to form a special network, I am 
unable to say. During the process of absorption it 
looks as if the fat which keeps penetrating farther and 
farther into the interior of the villi, filled up the whole 
parenchyma.* At last it reaches the central lacteal, and 
there the regular current of chyle begins. 

The whole process therefore presupposes an emulsive 
condition of the fat, which penetrates through the parts 


* I have quite recently convinced myself by the examination of transverse sec- 
tions of villi, filled with chyle, in man, that the fat does not lie scattered in the 
parenchyma, but forms deposits in the interior of special minute cavities (cells ?).— 
Note to the Second Edition. 





RETENTION OF CHYLE. 369 


everywhere in a state of extremely minute division ; in 
the regular course of events the particles are so ex- 
tremely minute, thatif the chyle is examined when fresh 
and still warm, scarcely a trace of the solid particles 
can be detected in it. But every disturbance which 
occurs in the process of absorption, and impedes the 
onward movement of the fatty particles, causes them to 
run together; larger granules separate in the tissues, 
drops appear which continually increase in volume, until 
at length they attain quite a large size. These are 
found even in the epithelial cells or within the tissue of 
the villi; and indeed it sometimes happens that the ends: 
of the lacteals grow wider, and swell out into a bulbous 
form from the great accumulations of fat, so as to be 
recognized even by the naked eye. Nowhere have they 
been so frequently witnessed in a striking form, as in 
cholera, and a good description of these appearances as 
occurring in this disease was published as far back as 
1837 by Bohn. They indicate nothing more than an 
obstruction to the current of lymph in consequence of 
the disturbances in the respiration and circulation (Fig. 
109, D). Since attacks of cholera are well known to 
occur with preponderating frequency during digestion 
and are attended by greatly impeded respiration, which 
makes itself felt throughout the whole venous system, 
they must of course also react upon the stream of chyle. 
Thus the enormous accumulation (retention) of fat in 
the villi is explained. This is therefore, if you will, a 
pathological condition, but, it only depends upon a tran- 
sitory obstruction, and we have every reason to suppose 
that, when the current again becomes free, these large 
drops of fat are gradually removed. But here we set 
foot upon other domains, where the boundaries of patho- 
logy can only be traced with great difficulty, and this is 


particularly the case with the liver. 
24 


370 LECTURE XV. 


It has been known from of old that the fiver is the 
organ, which is by far the most liable to fall into a state 
of fatty degeneration, and the knowledge of this state 
has long been derived from popular experiment. The 
history of the patés de foie gras proves this in the most. 
agreeable manner, although M. Lereboullet of Strasburg 
maintains that the fatty livers of geese are physiological 
ones, essentially different from the pathological ones 
which are not eaten, but only observed. However, I 
must confess that I have hitherto been unable to discover 
the difference between physiological and pathological fatty 
livers ; on the contrary, I believe that it is only by ad- 
mitting the identity of the two that correct notions with 
regard to the pathological fatty liver can be obtained. 
We are namely acquainted with a fact which was like- 
wise first observed by Kolliker, that in sucking animals, 
a few hours after digestion has taken place, a kind of 
fatty liver is a constant physiological occurrence. When 
of the same litter of animals some are made to fast, 
while others are allowed to suck, those which have 
sucked have a fatty liver a few hours afterwards, whilst 
the others have not. The fatty liver appears quite pale, 
though certainly not so white as a goose’s liver. This 
observation led me to examine the question of the rela- 
tion of the fat to the liver a little more minutely, and I cer- 
tainly think we may positively conclude that there does 
exist a close connection between the physiological and 
pathological forms. 

I found, namely, that a short time after the hepatic cells 
display this repletion with fat, a similar condition is found 
in the course of the biliary ducts, and that both in them 
and in the gall-bladder the epithelium presents the same 
appearances which we have witnessed in the intestinal epi- 
thelium during the absorption of fat. You only require 
therefore to invert the picture we just now considered 


ey: 
Sea 











FATTY LIVER. 371 


(Fig. 109) ; instead of a villus, invested externally with 
epithelial cells, imagine a canal clothed on the inside with. 
epithelium. The delicate cylindrical epithelium in the 
‘gall-bladder has the same striated border as that in the 
intestine (Fig. 14), and the fat is seen in the same way to 
penetrate into it from without, to pursue its course down- 
wards and after a time to pass into the wall of the gall- 
bladder. The same may be said of the biliary passages 
(duct. biliferi, hepat., cystic., choledoch.), which are also 
provided with cylindrical epithelium of a similar struc- 
ture. I have watched the same process also in young 
sucking animals after digestion, and there it is easy to 
convince oneself that the fat, which for a time is con- 
tained in the hepatic cells, is manifestly excreted from 
them into the biliary ducts, but that in the course of 
these ducts the fat is reabsorbed and thus a second time 
returns into the circulation. 

Such an intermediate interchange of matter as this, 
where the fat. passes from the intestine into the blood, 
from the blood into the liver, from the liver into the bile, 
and thence again into the lymphatics, or into the capilla- 
ries which conduct the blood back to the hepatic veins and 
to the heart, presupposes of course, just as absorption in 
. the intestines does, that the conveyance back again must 
take place under favourable circumstances ; if any dis- 
turbing cause arises, a retention will of course ensue, and 
the place of the fine granules will gradually be occupied 
by large drops. But this is the mode of proceeding as 
it can really be traced in the fatty liver. 

Upon studying a fatty liver, it is generally seen that 
the fat is first deposited in that zone of the acini which is 
immediately contiguous to the capillaries into which the 
branches of the portal vein break up (Fig, 110. ¢, c). 
When sections of the organ are carefully examined with 
the naked eye, it looks in many parts as if one had an 


3872 LECTURE XV. 


oak-leaf with its ribs and indentations before one ; the 
ramifications of the branches of the portal vein correspond 
to the ribs, the fatty zone to the sub- . 
stance of the leaf. The more abun- 
dant the infiltration, the broader does» 
the fatty zone become, and there are 
cases in which the fat fills the whole 
of the acini up the central (intralobu- 
lar) hepatic vein (Fig. 110, A) and 
every single cell is crammed full of 
fat. In rare cases it certainly happens, that we find just 
the reverse, and that the fat lies around the central 
vein ; these are cases which are probably to be explained 
by supposing that the fat is already in process of excre- 
tion and only the last cells still retain a little of it. Only 
we must take care not to confound with this condition a 
kind of fatty, necrobiotic atrophy which occurs particu- 
larly in chronic cyanosis.* | 

If now we consider the process in detail, we find that 
the manner in which the hepatic cells fill themselves, en- 
tirely corresponds to that, in which an epithelial cell in 
the intestine becomes filled with fat. At first we find 
fat-granules widely scattered, and indeed very small, 
They become more numerous, more closely aggregated, 
and after a time larger; at the same time the cells be- 


Fig. 110. 





Fig. 110. The adjoining halves of two hepatic acini. p. A branch of the portal 
vein with braches p’ p”, corresponding to the interlobular veins. h, h. Transverse 
sections of the intralobular, or hepatic, vein. a. The pigment zone, } the amyloid 
zone, ¢ the fat zone. 2 diameters. 


* Cyanosis (chronic) is here used to express the general venous congestion which 
is consequent upon chronic affections of the lungs and heart. ‘Since (as the Au- 
thor says in a MS. note) it has become known that cyanosis, even when produced 
by congenital malformation of the heart, does not arise from a commingling of 
arterial and venous blood, but from an obstruction to the venous circulation, it has 
seemed reasonable to designate every more general hyperemia, due to such ob- 
struction, by the same term.” ‘‘ Acute cyanosis,” he adds, ‘occurs in acute affec- 
tions of the lungs, as for example, in pertussis.” —Tr. 











FATTY LIVER. 373 


come larger, swell up, and larger and smaller drops of fat 
are found in them (Fig. 27, B, 6), until, when filled to 
the utmost, they present the same appearance as those 
of adipose tissue ; scarcely any membrane, and scarcely 
ever a nucleus is seen, nevertheless they both still con- 
tinue to exist. This is the condition which is called fatty 
liver, in the proper sense of the word. 

In it too we have what we found to be the case in adi- 
pose tissue—a persistence of the cells. There is no such 
thing as a fatty liver in which the cells have ceased to 
exist ; these constituents of the organs always exist, only 
they are almost entirely filled with drops of fat instead 
of with their ordinary contents. It can scarcely be 
doubted but that even in this condition they still contain 
a certain amount of matter capable of performing its 
functions. For in many animals, as for example the 
cod-fish from which liver-oil is obtained, the functions. of 
the organ are still performed, however large the quantity 
of oil contained in the cells. In man too, even in the 
most advanced stage of fatty liver, we still find bile in the 
gall-bladder. So far therefore these conditions can in no 
respect be compared to the necrobiotic conditions, which 
are found in the course of fatty degeneration in so many 
other parts, and in which the elements perish. In fatty 
degeneration, in the ordinary sense of the word, we find, 
in the later stages of the affection, somewhere or other, 
friable, softened places, where the fat is contained in free 
drops—in some sort fatty abscesses.. It is therefore a 
fact of extreme importance, and one which I consider to 
afford very decided indications for the correct apprecia- 
tion of this form [fatty liver], that in it there is always a 
persistence of the histological constituents, and that, how- 
ever much these constituents may become filled with 
foreign substances, they still continue to exist as cells. 
Hence it follows, that a fatty condition of the liver may 


874 LECTURE XY. 


be removed, that it is curable, without any particular. 


regenerative processes being required for the cure. The 
only requisite is, that the causes of the retention be re- 
moved, and the hepatic cells be freed from fat. It is true 


we have no positive information respecting either the one 


or the other of these points. We are not acquainted with 
the states which lead to the retention of the fat, nor with 
the conditions under which it can again be expelled. 
However, now that we have got so far, it will probably 
also be possible to make out the remaining facts. For it 
is conceivable, for example, that simply the elasticity of 
the histological elements is of importance ; that when the 
cell walls become relaxed, they may readily admit a 
quantity of matter, and tolerate its presence in them, 
whilst, if they are very elastic, a removal, an expression 
of their contents, may be more likely to ensue. The 
state of the circulation also is certainly of importance, 
and the frequent occurrence of fatty liver in chronic affec- 
tions of the lungs and heart is certainly in no small de- 
gree to be ascribed to the increased pressure to which 
the venous blood is subjected. 

What I was particularly anxious, gentlemen, to render 
evident to you, was the great difference which this kind 
of fatty degeneration presents from that which we have 
previously considered. Whilst there we saw arise be- 
tween the proper specific constituents of the organ—fat- 
cells which belonged to the connective tissue, here it is 
the specific gland cells themselves which are the seat of 
the fat. On the other hand, you must take into consider- 
ation the great difference from the necrobiotic processes 
of fatty degeneration, in which the cells as such disap- 
pear. 

We have now, gentlemen, to consider this third series 
of fatty gonditions a little more closely, those, I mean, 
which are attended by a destruction of the elements, and 














FORMATION OF SEBACEOUS MATTER. 875 


of which we have set up the secretion of milk and seba- 
 ceous matter as the true types. That these two secre-. 
tions are analogous to one another, is simply explained 
by the circumstance that the mammary gland is really 
nothing more than an enormously developed and pecu- 
liarly formed accumulation of cutaneous (sebaceous) 
glands. In their development both classes are perfectly 
analogous. Both are produced, by means of a progres- 
sive proliferation, from the internal layers of the epider- 
mis (p. 68, Fig. 18, A). To the same category also be- 
long the ceruminous glands of the ear, and the large 
glands of the axilla. In all these 
cases the fat, which constitutes the Fis. 111. 
chief constituent of milk, at least as 
far as its external appearance is 
concerned, and which furnishes the 
sebaceous secretion, originates in 
the interior of epithelial cells 
which gradually perish and set the 
fat free, whilst scarcely a trace of 
the cells is preserved. The se- 
baceous glands are generally seated 
‘on the sides of the hair-follicles 
at some depth below the surface ; 
we there find a series of mi- 
nute lobules, into which a prolon- 
gation of the rete mucosum is un- 
interruptedly continued. The cells 
of this become more numerous and 
larger, so as to fill the gland-sacs 
with a nearly solid matter. Then the fat begins to be 





Fig. 111. Hair-follicle with sebaceous glands from the skin. ec. The hair, 5 its 
bulb, e, e, the layers of cells dipping down from the epidermis into the hair-follicle. 
g g. Sebaceous glands in the act of secreting sebaceous matter; at /, the secretion 
mounting up by the side of the hair and accumulating. 280 diameters, 


376 LECTURE XV. 


secreted into their interior, at first in small particles, 
which soon become larger, and after a short time the 
individual cells can no longer be distinctly perceived, 
but only conglomerations of large drops, which rise up 
out of the gland into the hair-follicle. If we unravel 
the gland so as to form a flat surface, its layers of cells 
would have the appearance of epidermis, only that the 
oldest cells do not become horny, but are destroyed by 
fatty metamorphosis. The secretion is a purely epi- 
thelial one, like the seminal secretion. 

This process furnishes us at the same time with an 
accurate representation of the formation of milk. You 
need only imagine the ducts much lengthened, and the 
terminal acini greatly developed; the process remains 
essentially the same: the cells multiply abundantly ; the 
multiplied cells undergo fatty degeneration, and ulti- 
mately there remains scarcely any material traces of 
these cells excepting the drops of fat. The closest re- 
semblance to the manner in which the secretion of seba- 
ceous matter ordinarily takes place, is presented by the 
earliest. period of lactation when the so-called colostrum 
is ylelded. A colostrum-corpuscle (Fig. 112, C’) is the 
still coherent globule which results from the fatty de- 
generation of an epithelial cell. The formation of colos- 


BIG TQ: 





Fig. 112. Mammary gland during lactation, and milk. .A. Lobule of the mam-' 
mary gland, with milk issuing out of it. B. Milk globules. @. Colostrum, a, a dis- 
tinct fat-granule cell, 6, the same with evanescent nucleus. 280 diameters. 


COLOSTRUM- AND MILK-CORPUSCLES. 377 


trum and sebaceous matter differs in this respect only, 
that the fat-granules remain smaller in the former case, 
and that whilst large drops very soon show themselves 
in sebaceous matter, in colostrum the last cells which 
are observed, usually contain only minute fat-granules, 
very densely aggregated, whereby the whole cell ac- 
quires a somewhat brownish appearance, although the 
fat has no actual colour. This is the granular corpuscle 
(corps granuleux) of Donné. 7 

Foi the discovery of this gradual transformation of 
cellular bodies into fat-granule masses we are indebted 
to Reinhardt. Still he shrank from extending this 
important discovery of the formation of colostrum. to 
the history of milk in general, for the reason, that, 
during the later periods of lactation properly so-called, 
granulated bodies are no longer met with. It is, how- 
ever, unquestionable, that between the earlier formation 
of colostrum-corpuscles and the later one of milk, there 
is no other difference than this, that in the formation of 
colostrum the process goes on more slowly, and that the 
cells maintain their cohesion longer, whilst in the secre- 
tion of milk the process is acute and the cells more 
speedily perish. Perfectly developed colostrum con- 
tains an extremely large number of granulated cor- 
puscles, milk nothing more than a number of compara- 
tively large and small drops of fat, mixed up together, 
the so-called mulk-corpuscles (Fig. 112, B), which are 
nothing more than drops of fat, and like the majority of 
the drops of fat that occur in the animal body are sur- 
rounded by a delicate, albuminous membrane, called by 
Ascherson the haptogenic* membrane (haptogenmem- 
bran). But the individual drops (milk-corpuscles) cor- 
respond to the drops which we find in the secretion of 


* J. e., produced by contact.—Transt, 


378 LECTURE XV. 


sebaceous matter ; they are produced by the coalescence 
of the minute granules which appear in the secretion of 
colostrum. 

Now that we have seen these types of physiological 
transformation, gentlemen, the description of the patho- 
logical changes no longer offers any difficulty. With 
the exception of very few structures, as for example, 
red blood-corpuscles and the nerve-fibres in the great 
nervous centres, nearly all other cellular parts may 
under certain circumstances undergo a similar metamor- 
phosis, which displays itself in a precisely similar man- 
ner, that is, isolated, extremely minute globules of fat 
appear in the cell-contents, become more abundant, and 
gradually fill up the cell-cavity, without, however, run- 
ning together into such large drops, as is the case in 
fatty infiltration and in the adipose-tissue formations. 
Usually, the development of the fat-granules first de- 
clares itself at some distance from the nucleus; very 
seldom does it begin at the nucleus. This is the cell 
which has long been called the granule-cell. Then 
comes a stage, in which the nucleus and membrane are 
indeed still to be seen, but the fat-granules lie as close 
to one another as in colostrum corpuscles ; only at the 
spot where the nucleus lay, there is still a little gap 
(Fig. 66, 6). From this stage there is but a short step 
to the complete destruction of the cell. For a cell 
never remains for any length of time in the state of a 
granule-cell, but as soon as it has once entered into this 
stage, the nucleus generally disappears at once, and 
ultimately the membrane also, probably by a species of 
solution. Then we have the simple granule-globule, or as 
it was formerly called, znflammatory globule [exudation- 
corpuscle], which Gluge first described under this name 
(Wig. 66,.¢2), 

Gluge in this made one of those mistakes which not 


GRANULE-CELLS—GLOBULES. 379 


unfrequently marked the early periods of microscopy. 
He saw, when examining a kidney, bodies of this sort 
in the interior of a canal, which he took for a blood- 
vessel ; this happening at a time when the doctrine of 
stasis was most in vogue, he imagined he had before 
him a vessel with stagnating contents which were disin- 
tegrating, and generating inflammatery globules. Un- 
fortunately the blood-vessel was a uriniferous tubule ; 
what he took to be parts of disintegrating blood-corpu- 
scles, was fat; and what he called inflammatory glo- 
bules, fatty degenerated renal epithelium. One might 
easily have spared oneself this error in the history of 
stasis, but at that time there were few people who knew 
what was the appearance of uriniferous tubules and 
how they might be distinguished from vessels, and thus 
some time elapsed before this theory of inflammation 
was put down. 

At present we call the body a granule-globule and 
regard it as the first distinct proof of degeneration, 
when the cell no longer retains its existence as a cell, 
but merely its former shape remains, after the parts 
which really constitute a cell, namely the membrane and 
the nucleus, have completely passed away. After this, 
in accordance with external circumstances, either a com- 
plete destruction of the parts ensues, or they may still 
persist, coherent. If, namely, we have to deal with very 
soft parts, in which much fluid or juice has been present 
all along, the granules fall asunder. The medium 
which bound them together and enabled them to retain 
the globular form, namely, a remnant of the old cell- 
contents, is gradually dissolved. The globule breaks up 
into a crumbling mass, which is often still somewhat co- 
herent in places, but from which one drop of fat after 
another is detached, so that the correspondence with 
milk is very beautifully displayed. 


380 LECTURE XV. 


This is the manner in which the disintegration of 
nearly all parts takes place, which essentially consist of 
cells and naturally contain a good deal of fluid, as for 
example pus among familiar pathological products 
(p. 216, Fig. 66). If, on the contrary, the parts are in 
themselves somewhat more rigid, so that movement in 
and displacement of, the fatty mass takes place with less 
facility, the fat remains in the form of the previous cell. 
Of this we meet with an example in the fatty degenera- 
tion of the walls of arteries. 

In the aorta, the carotids and the cerebral arteries, 
changes of the inner coat are often seen with the naked 
eye of such a nature, that small, whitish spots of a 
rounded or angular form, occasionally running one 
into the other, project somewhat above the surface. 
If an incision is made at these spots, it is found that 
they are quite superficial, that they lie in the innermost 
layer of the internal coat and must not be confounded 
with the really atheromatous condition. If such a spot 
be cut out, it is found that a fatty degeneration of the 
connective-tissue-corpuscles of the innermost coat has 
taken place ; and since they are branched cells, we do 
not here have granule-cells in their ordinary rounded 
form, but often very long, fine bodies, which here and 
there swell up into the form of a spindle or star, and in 
which the fat-granules lie heaped up like strings of 
pearls, whilst between there still remains intermediate 
substance quite intact. It is the cellular elements of the 
connective tissue which in these cases undergo the 
change in their totality. Afterwards the intermediate 
substance also softens, the cellular fat-granule masses 
fall asunder, and the current of blood carries away the 
particles of fat with it. In this way a number of un- 
even places are produced upon the surface of the vessel, 
which swell up as long as the process continues, after- 


FATTY METAMORPHOSIS. 3881 


wards become worn away (usurirt), and acquire a slightly 
velvety appearance, without there being any ulceration 





in the proper sense of the word. This is a particular 
form of fatty usure which occurs in many parts, as for 
example in articular cartilages, and even on the surface 
of mucous membranes, for example, that of the stomach 
(Fox). But at no time does the matter accumulate in 
such abundance as is the case in abcesses which have 
undergone fatty degeneration. If, on the other hand, a 
similar. process commences beneath the surface, as in 
the atheromatous process, the fatty degeneration then 
proceeds from below upwards, and the surface is not 
reached until the last. By softening, the so-called athe- 
romatous deposit (Heerd*) is produced, which contains a 
softened mass resembling the contents of atheromata 
[sebaceous,} or epidermic, cysts] of the skin, in which 


Fig. 113. Fatty degeneration of cerebral arteries. A. Fatty metamorphosis of the 
muscular cells of the circular-fibre coat. B. Formation of fat-granule cells in the 
connective-tissue-corpuscles of the internal coat. 3800 diameters. 


* Heerd (hearth) in the sense in which it is here employed, has no precise equiva- 
lent in English, although it exactly corresponds to the French foyer. ‘‘ It denotes,” 
says the Author, ‘‘ the spot, where the fire of the disease burns, but expresses at the 
same time that this spot is a limited one.” I have therefore translated it by various 
words, such as deposit, dép6t, seat (of the disease), collection, patch (atheromatous), 
focus, &c.—TRANSL. 

+ These cysts are wrongly called sebaceous, inasmuch as they are essentially 
epidermic, and are generally derived, not from the sebaceous glands, but from the 
hair-follicles. The atheromatous matter is in these cases chiefly composed of degene- 
rated and disintegrated epithelium.—From a MS. Note by the Author. 


389 : LECTURE XV. 


the mixture of sebaceous matter and epidermis pro- 
duces a pultaceous mass. What we find in the arteries 
is a mixture of fatty débris with softened intermediate 
substance ; and, since the fatty mass is shut off, a kind 
of enclosed deposit results—as it were an abscess. It 
is only after the softening has proceeded to some extent 
that the surface gives way, and matters issue from the 
cavity into the vessel, whilst others proceed from the 
blood into the cavity. 

In this manner destruction, demolition, ulceration is 
produced, and ultimately the atheromatous ulcer, a species 
of ulcer very nearly allied to the ordinary forms of ul- 
ceration, but indebted for its origin to fatty metamor- 
phosis alone. It is a product of the [atheromatous]. 
deposit, but it no longer contains any formed elementary 
parts. Cholestearine indeed may still be set free, but 
we have really and truly to deal with a destructive and 
ultimately ulcerative process. It is only in those parts, 
in which, as in the mammary and sebaceous glands, there 
is a succession of new cells, that the process of fatty 
metamorphosis can continue for any length of time 
without leading to such an annihilating result. But, 
even in these instances, the different cells affected ulti- 
mately perish and break up, as in the really fatty de- 
generation. 





Lie Lb oN i eV 
APRIL 14, 1858. 
A MORE PRECISE ACCOUNT OF FATTY METAMORPHOSIS. 


Fatty degeneration of muscles—Fatty metamorphosis of the substance of the heart 
—Formation of fat in the muscles in distortions, 


' Corpus luteum of the ovary—Fatty metamorphosis of pulmonary epithelium—Yel- 


low softening of the brain—Arcus senilis. 

Optical properties of fattily degenerated tissues—Renal epithelium in Bright’s dis- 
ease—Successive stages (cloudy swelling, fatty metamorphosis, fatty detritus 
[débris], atrophy)—Inflammatory globules—Similarity of the result in inflam- 
matory and non-inflammatory changes. 

Atheromatous process in arteries—Its relation to ossification—Inflammatory cha- 
racter of the process; its analogy with endocarditis—Formation of the athe- 
romatous deposit—Appearance of cholestearine—Arterio-sclerosis—Endoarte- 
ritis—Calcification and ossification of arteries. 

Mixed, activo-passive processes, 


To-pay, gentlemen, I have sent round afew specimens 
of fatty degenerations, in part to serve as a supplement 
to what you saw at the last lecture. 

One or two of these preparations are intended to dis- 
play the fatty degeneration of the substance of the heart. 
You will observe that, even with the naked eye, certain 
changes can be recognized in the heart, namely, a disco- 
loration of its whole substance (which no longer presents 
the red hue of muscle, but wears a pale yellow tint), and 
besides peculiar spots on the papillary muscles. If you 
examine these more closely, you will perceive, in the 
direction of the primitive fasciculi, short, yellowish 

883 


384 LECTURE XVI. 


streaks which communicate so as almost to present a 
plexiform arrangement, and pervade the substance of the 
papillary muscles, whilst they offer a striking contrast. to 
the reddish colour of proper muscular substance. This 
is the perfect form of genuine fatty metamosphoris of the ~ 
real muscular substance of the 
heart, which differs most essentially 
from obesity of the heart, in which 
this organ becomes extremely fat 
and adipose tissue here and there 
so infiltrates its walls, that scarcely 
any muscle is to be perceived. Be- 
tween the two conditions there 
always remains the notable diffe- 
rence, that in the former case whole 
portions of active substance are 
interrupted by parts which are manifestly no longer 
capable of action. 

I have besides brought you another specimen of mus- 
cle we obtained yesterday at the suggestion of our con- 
frére Berend. <A body, namely, with posterior (angular) 
and lateral curvature (Kypho-Skoliose) was brought for 
post-mortem examination, and, when we examined the 
muscles at the point of curvature, we found the longissi- 
mus dorsi at the spot where it passed over the projec- 
tion, converted into quite a flat, thin, pale yellowish 
mass. At one point the muscle has, with the exception 
of a membranous layer, entirely disappeared, its red hue 
has altogether vanished ; towards the lower part the 
muscle also presents an abnormal appearance, but there 
it is composed of alternate longitudinal red and yellow 
streaks. This is the form exhibited by most fattily de- 
generated muscles which we find in distortions of the 


* Fig. 114. Fatty degeneration of the muscular substance of the heart in its dif- 
ferent stages. 3800 diameters. 


Fig. 114, 






ve 
= 
4-2 








ox — 
Saas 


= 
> a 
mee RO 


SS 
SSS 
Sa 
peer 
ea 
SKeeriscn- 
SSI a5 Sr 





FATTY DEGENERATION OF MUSCLES. 885 


limbs, as for example, in the different kinds of club-foot. 
In these it generally turns out, that, in the parts corres- 
ponding to the yellow streaks, there is not only a real 
transformation of the muscular substance, but that an in- 
terstitial development of adipose tissue has also nearly 
constantly taken place there, so that it lies in rows be- 
tween the primitive muscular fasciculi, and thereby pro- 


‘duces a striation which looks yellowish to the naked eye, 


and is due to an arrangement very similar to that which 
gives rise to the red striation of genuine muscular tissue.* 
This is precisely how matters stood in the case I spoke 
of recently (p. 864, Fig. 108), where we found a row of 
fat-cells between every two primitive fasciculi ; the yel- 
low that you saw there, was not altered muscle, but a 
mass of fat which had grown in between the muscular 
fibres. But in addition to such interstitial adipose tissue 
there is in the case now before us a parenchymatous de- 
generation in the same muscle ; the substance of the mus- 
cle is also really in a state of fatty degeneration. The 
degenerated fibres are, however, only to be seen with 
the naked eye in the lower parts of the muscle, whilst 
the portion which lay in immediate contact with the 
greatest projection of the thorax and had been subjected 
to the greatest tension, to the naked eye presents no 
trace of muscular tissue. Under the microscope, how- 
ever, we even there find isolated muscular fibres lying 
close to one another and still distinctly transversely stri- 
ated, and others plentifully filled with fat. You see, 
therefore, that these are two different conditions; the 
one form, where the muscle is interrupted in the course 
of its primitive fasciculi by degenerated places, and where 

* For, as each row of fat-cells lies between two primitive fasciculi (Fig. 108), the 
fat (like the substance of the fasciculi, the cyntonine) has a layer of sarcolemma 
upon each side of it, so that, if the syntonine atrophies, the fat appears to have 
taken its place and to lie within the primitive fasciculi, and many well-known au- 


thors have taken this to be the case.—From a MS. Note by the Author. 
25 


386 LECTURE XVI. 


therefore the same primitive fasciculus, is, as it pursues 
its course, now in a state of degeneration, now preserved 
in all its integrity ; the other form in which the disease 
sweeps along the primitive fasciculus, and this undergoes 
the change in its whole extent at once, and where there- 
fore normal and degenerated fasciculi lie side by side, 
and may alternate with one another. 

Here is another specimen from a young female (who 
died shortly after menstruation in consequence of a burn) 
in which you will find a very beautiful corpus luteum in 
the ovary. I lay it before you because you will be able 
to see, from it, how obviously fatty metamorphosis may 
display itself to the unaided eye. The incision into the 
ovary has been made perpendicularly to the surface, at a 
point where a little prominence and slight rent upon the 
surface mark the place at which the ovule has emerged 
(Fig. 115, B). From the point in the tunica albuginea 
where the follicle has burst, the very broad, yellowish 


MEGS AEG: 





white layer (Fig. 115, A, 5), from which the body derives 


its name, is seen running around a red mass. It is this 


Fig. 115. Formation of corpora lutea in the human ovary. A. Section of an 
ovary: a, a follicle recently burst and filled with coagulated blood (extravasation, 
thrombus), and around it the thin yellow layer; 6, a follicle, which had burst at an 
earlier period, already corrugated, and provided with a diminished thrombus and 
thickened wall; c, da still more advanced stage of retrogressive metamorphosis. | 
B. External surface of the ovary, with the fresh rent caused by the bursting of the 
follicle, from the cavity of which the thrombus is seen peeping out, Natural size. 





= 


FATTY METAMORPHOSIS OF PULMONARY EPITHELIUM. 387 


layer which, in a puerperal corpus luteum, is of very 
great breadth and has a rather reddish yellow tint ; in a 
menstrual corpus luteum it is narrower, and very dis- 
tinctly separated on the inner side from the freshly ex- 
travasated contents which have filled up the follicle emp-— 
tied by the extrusion of the ovule. This internal red 
mass: consists entirely of thrombus, or blood-clot. The 
external layer essentially consists of fattily degenerated 
cells, and the yellow colour which it bears is occasioned 
by the refraction produced by the numerous minute par- 
ticles of fat. This is not a real colour, but a phenome- 
non of interference. 

A similar change you see in a lung which we took to- 
day out of the body of a man who, after caries of the in- 
ternal ear, had a thrombosis of the transverse sinus with 
gangrenous metamorphosis, and, in consequence, gan- 
grene of the lung. The cells we have here to deal with 
were not taken, however, from the actual seat of the gan- 
grene itself, but from a condensed spot in the neighbour- 
hood, where a very abundant accumulation of masses of 
proliferating epithelium (catarrhal pneumonia) had taken 
place. In this case you can see the difference between 
fat-granule-cells (Fig. 66), and other forms of granule- 
cells, very prettily shown. For in these masses of epi- 
thelium which have filled up the alveoli of the lung, you 
find extremely numerous pigment-cells, such as in cases 
like this are brought up in great quantity in the sputa, 
which are indebted to them for the well-known smoky 
grey spots (Fig. 11, 6). A# first sight it is difficult to 
make a distinction between fat-granule-, and pigment- 
cells, inasmuch as in both cases apparently the same 
image is offered to our view. In the one case the cells 
appear as brownish yellow corpuscles, although their indi- 
vidual particles have no positive colour ; in the other, on 
the contrary, they contain unquestionable, grey, brown, 


388 LECTURE XVI. 


or black, pigment. The diagnosis of ordinary granule- 
cells, by which fat-granule-cells are always meant, is, 
however, very important, because in other parts also, as 
for example, in the brain, we find both sorts of granule- 
cells, those containing fat and those containing pigment, 
side by side ; and even when the affection is limited to 
very small spots in this organ, it 1s very important™ for 
the interpretation of the objects found to know whether 
they belong to the one or the other class. For in the 
brain also the accumulation of a number of minute par- 
ticles of fat may on the whole, through the multiplication 
of the refracting points, occasion an intense yellow colour. 
The different proportion of fat and the degree of its divi- 
sion produce a greater number of varieties of colour which | 
at last manifest themselves very distinctly to the naked 
eye, so that the more minute and the more closely ag- 
gregated the fatty particles are, the more marked is the 
production of a pure yellow or brownish-yellow hue even 
to the naked eye. What we call yellow softening of the 
brain is also really nothing more than a form of fatty de- 
generation, where the yellow appearance of the affected 
spot is owing to the accumulation of finely granular fat. 
As soon as this is removed, the colour also disappears, 
although the fat thus extracted is by no means of so deep 
a hue as the spot whence it was derived. The refraction 
of light between the extremely minute particles is the 
chief cause of this phenomenon of colour. 

It is self-evident that at every point, where the fatty | 
degeneration attains a high pitch, great opacity will 
always present itself. A transparent part becomes 
opaque when it undergoes fatty degeneration ; this we 
see, for example, in the cornea, the fatty clouding of 
which may become so marked in arcus senilis, that an en- 


* Eor the pigment would point to apoplexy, the fat to softening. 











FATTY DEGENERATION OF RENAL EPITHELIUM. 889 


tirely opaque zone is thereby produced. Even in places, 
where the parts were originally not transparent, but 
only translucent, a complete opacity may be seen to de- 
clare itself in proportion as the process of fatty degene- 
ration progresses. 

Consider, for example, a kidney in the stage of fatty 
degeneration. I show you here a preparation which 
does not present the ordinary. granular atrophy of 
Bright’s disease, but a more chronic and smooth form. 
The convoluted uriniferous tubules of the cortex are 
very much enlarged, and the whole of its epithelium is 
in a state of fatty degeneration, so that within the tu- 
_bules there is really nothing else to be seen than a 
densely crowded mass of fat-granules. If however 
microscopical sections are very carefully prepared, the 
fat-granules are in the first instance still seen collected 
in isolated groups (as granule-cells or granule-globules, 
Fig. 98); but upon slight pressure the mass disperses in 
such a way, that the whole uriniferous tubule is uni- 
formly filled with finely emulsive contents. Even with 
the naked eye you can distinctly recognize the change ; 
and as soon as one has become accustomed to discri- 
minate with some degree of accuracy between these 
less obvious conditions, there is not the slightest diffi- 
culty in discovering from the aspect of such a part the 
presence of a change in the renal epithelium, and that 
indeed of this particular kind, for there is no other form 
of change which could be compared to it. If you 
examine the surface of the kidney you will perceive 
that over the rather greyish, transculent ground, upon 
which the Stellula Verheynii* stand out, small opaque - 
spots are scatterred in the most varied manner, most of 
them forming not real points, but usually small segments 
of an arc. These will always be found to. be parts of 


* The stellate veins. —TRANSL. 


390 LECTURE XVI. 


the convolutions of uriniferous tubules which have 
mounted up to the surface. These yellowish, opaque- 
looking convolutions correspond to fattily degenerated 


uriniferous tubules, or to speak more accurately, to 


uriniferous tubules filled with fattily degenerated epithe- 
lium. If a section be compared with the surface, the 
same markings are very distinctly seen to run through 
the whole of the cortex, from the periphery down to the 
upper borders of the medullary cones, and to invest the 
individual cones formed by the tubuli recti which are 
prolonged into the cortical substance—at pretty regular 
intervals. | 

If sections are made in such a case in the neighbour- 
hood of the surface and parallel to it, we readily obtain 
a view embracing the fattily degenerated tubules by the 
side of more normal ones, and of unaffected glomeruli. 
With a lower power and by transmitted light, we see 
close to the Malpighian bodies which appear as large, 
light, globular structures, the convolutions of the de- 
generated uriniferous tubules interlacing in various ways, 
and the convoluted tubules distinguished by their opaque, 
shaded appearance from the straight ones, which are 
lighter and more translucent. 

I will here call your attention to the circumstance, 
that in all fatty parts, where, by reflected light and as we 
usually view objects with the naked eye, we see whitish, 
yellowish, or brownish-yellow parts—by transmitted 
light, as generally employed for microscopes, and espe- 
cially with the higher powers, either black, or brownish 
black, or at least very dark parts, surrounded by 
sharply-defined shadows, appear. <A  granule-globule 
which, when lying together with several others, pro- 
duces a spot white and opaque to the naked eye, will, 
when viewed by transmitted light, display a nearly black 
appearance. 


GENUINE FATTY METAMORPHOSIS. 394 


We have now compared a series of examples of fatty 
degeneration, and may henceforth confine ourselves to 
the consideration of genuine fatty metamorphosis, in 
which the normal structure of the part is ultimately 
destroyed, and the place of the histological elements is 
gradually occupied by a purely emulsive mass, or, more 
concisely, fatty debris. It makes no difference whether 
it is a pus-cell, a connective-tissue-corpuscle, a nerve- or 
muscular fibre, or a vessel which experiences the change ; 
the result is always the same; namely, milky débris, 
an amorphous accumulation of fatty particles in a more 
or less highly albuminous fluid. But though we hold to 
the agreement of all cases of fatty metamorphosis in 
this respect, it by no means, however, follows that the 
importance of this change as a morbid process is in 
every case the same. This you may at once infer from 
the circumstance, that, whilst I have introduced this 
process to your notice in the category of purely passive 
disturbances, one of the very structures which we most 
frequently find in it, the granule-globule, has been re- 
garded as a specific element of inflammation. For 
years an inflammatory globule [exudation corpuscle] 
was looked upon as an essential phenomenon in the 
process of inflammation, and in fact, the frequency with 
which cells in a state of fatty degeneration are found in 
inflamed parts, affords sufficient proof, that in the course 
of inflammatory processes, which it is impossible we 
should ever regard as simply passive processes, such 
transformations must take place. It is therefore very 
essential to find a means of distinguishing between the 
two classes. This offers indeed in particular cases very 
great difficulties, and according to my conviction the 
only possible method by which clear notions upon the 
subject can be obtained, consists in examining whether 
the condition of fatty degeneration is a primary or se- 


392 LECTURE XVI. 


condary one, whether it sets in as soon as the distur- 
bance can be perceived, or whether it does not occur 
until some other perceptible disturbance has gone before. 
Secondary fatty degeneration, or that in which this 
peculiar transformation occurs only in the second place, 
generally succeeds to a first and active stage ; a whole 
series of those processes which we do not scruple to call 
inflammations run their course in such a way, that a 
fatty metamorphosis sets in as the second or third ana- 
tomical stage of the change. Here therefore the fatty 
degeneration does not arise as a direct result of the 
irritation of the part, but where we have the opportu- 
nity of more accurately tracing the history of the 
changes, it nearly always turns out, that the stage of 
fatty degeneration has been preceded by another stage, 
namely that of cloudy swelling, in which the parts 
enlarge and increase in extent and density, in conse- 
quence of their absorbing a large quantity of matter 
into themselves. Absorbing I say advisedly, because L 
hold it to be untrue that the part is in any way forced 
by external influences to take up this matter, or that it 
is inundated with exudation proceeding from the vessels, 
for the same phenomena present themselves also in 
parts which have no vessels. It is only when the ac- 
cumulation has attained such dimensions, that the 
natural constitution of the part is thereby endangered, 
that a fatty disintegration is set up in the interior of 
the elements. Thus we may designate fatty degenera- 
tion of the renal epithelium as a stage of Bright’s dis- 
ease (or as I say, parenchymatous nephritis), which has 
been preceded by a stage of hyperemia and swelling, 
in which every epithelial cell accumulated a large 
quantity of cloudy matter in itself, without there having 
been originally a trace of a drop of fat observable. 
Thus we see that a muscle under the influence of 











INFLAMMATORY FATTY DEGENERATION. 8938 ° 


agencies which it is universally conceded produce in- 
flammation, as for example after wounds, and chemical 
corrosions, swells up, that its primitive fasciculi become 
broader and more clouded, and that as a second stage 
the same fatty degeneration commences in them, which 
at other times we see primarily arise. 

It may therefore certainly, when quite general terms 
are used, be said, that there does exist an inflammatory 
form of fatty degeneration ; still, strictly speaking, this 
inflammatory form is never anything more than a later 
stage, a termination, which announces the commencing 
disintegration of the structure of the tissue, when the 
part is no longer in a condition to continue a separate 
existence, but is to such an extent abandoned to the 
play of the chemical forces of its constituent parts, that 
the next result is its really complete dissolution. Now 
inflammatory conditions of this kind are of very great 
importance, because in all parts whose essential ele- 
ments become changed in this manner, no immediate 
restitution is possible. When inflammation takes place 
in a muscle and in its course the primitive muscu- 
lar fasciculi fall into a state of fatty degeneration, as a 
rule they also perish, and we afterwards find a loss of 
substance in the muscle at the spot where the degenera- 
tion took place. The kidney, whose epithelium has 
passed into a state of fatty degeneration, nearly always 
shrivels up, and the result is a permanent atrophy. In 
exceptional cases something perhaps occurs, which 


reminds us of a regeneration of the epithelium, but 


usually a collapse of the entire structure ensues. 
The same thing is witnessed in the brain in yellow 
softening, no matter how it may have been. caused. 
Whether there have been inflammation or not, a va- 
cuity is formed, which is never again filled up with 
nervous matter. Perhaps a simple fluid may replace 


394 LECTURE XVI. 


the wanting tissues, but as to any reproduction of a 
new, functionally active part, that must ever be out of 
the question. 


Herein you must seek the explanation of the circum- 
stance, that conditions apparently very similar, and 


which from a _pathologico-anatomical point of view 
might be declared to be identical, in a clinical point of 
view lie widely apart, and that the same forms of 
changes are met with in analogous parts, without, how- 
ever the whole process, to which they belong, being the 
same. When a muscle falls into a state of simple fatty 
degeneration, its primitive muscular fasciculi may have 
just the same appearance as if inflammation or perma- 
nent tension had acted upon it. Myocarditis generates 
forms of fatty degeneration in the substance of the 
heart altogether analogous to those due to excessive 
dilatation of the cardiac cavities. When one of these, for 
example, either through some obstruction to the current 
of the blood, or from insufficiency of the valves, is per- 
manently much dilated, fatty degeneration of the muscu- 
lar tissue constantly manifests itself in the part which 
has been most stretched. This form, morphologically 
speaking, completely resembles the early stages of my- 
ocarditis, and in many cases it is utterly impossible 
to say with certainty in what way the process may 
have arisen. 

I have, in order to clear up to some extent these diffi- 
culties, as they are presented by an important, frequent 


and at the same time much misunderstood process, pre- 


pared a series of specimens exhibiting really atheromatous 
conditions of the arteries. For it is particularly in the 
case of these conditions that the confusion, which has pre- 
vailed with regard to the interpretation of the change, 
has perhaps been the greatest. 

At no period in the course of this century has a com- 








ATHEROMATOUS AFFECTION OF ARTERIES. 395 


plete understanding ever been come to as to what was to 
be understood by the expression atheromatous change in 
a vessel. Some have taken the term in a wider, others 
in a narrower sense, but still it has perhaps been taken 
in too wide a sense by all. When, namely, the anato- 
mists of the last century applied the name of atheroma 
to a definite change in the coats of arteries, they of 
course had in their minds a condition similar to that of 
the skin, to which ever since the days of ancient Greece, 
the name of atheroma, grit-follicle, (Griitzbalg) [sebace- 
ous or epidermic cyst], had been assigned. It is self- 
evident, therefore, that the idea of atheroma presupposes 
a closed sack. Nobody ever called anything in the skin 
an atheroma that lay open and uncovered. It was there- 
fore a curious misapprehension when people recently be- 
gan to call changes in the vessels atheromata, which were 
not seated below the surface and shut off from the sur- 
rounding parts, but belonged to the surface. Thus it has 
come to pass that, instead of an enclosed deposit being, 
in accordance with the original meaning of the term, 
called atheromatous, a change has frequently been so 
termed which commences quite at the surface of the in- 
ternal arterial coat. When the matter began to be exa- 
mined more minutely, and fatty particles (Fig.113) were 
found at very different points in the walls of the vessels, 
both when atheroma was, and was not, present—when 
at last the conviction was obtained, that the process of 
fatty degeneration was always the same and was identi- 
cal with the atheromatous change, it became the custom 
to unite all the forms of the fatty degeneration of arte- 
ries under the designation atheroma. Gradually, peo- 
ple even came to speak of an atheromatous change in 
vessels, that only possessed a single coat, for in them too 
we meet with fatty processes. 

At all times there have moreover been observers who 


396 LECTURE XVI. 


regarded the ossification of vessels as a change belonging 
to the same category as atheroma. Haller and Crell be- 
lieved that the ossification proceeded from the athero- 
matous matter, and that this was a juice which, like that 
exuding under the periosteum of bone, was capable of - 
generating plates of bone out of itself. Afterwards it 
was recognized that atheromasia and ossification were two 
parallel processes, which, however, might be referred to 
a common origin. Now it would, I think, have been 
logical, if in the next place an understanding had been 
come to as to what this origin was, from which the athe- 
romatous change and the ossification proceeded. But, 
instead of this, the track of fatty degeneration was pur- 
sued, and thus the atheromatous process was extended 
to a number of vessels, in which, on account of the thin- 
ness and the simple structure of their walls, the forma- 
tion of any dépdt, which could really be compared to an 
atheromatous cyst of the skin, was altogether impossible. 

The state of the matter here also is more or less very 
simply this, that two processes must be distinguished in 
the vessels, which are very analogous in their ultimate 
results ; first, the semple fatty metamorphosis, which sets 
In without any discoverable preliminary stage, and in 
which the existing histological elements pass directly into 
astate of fatty degeneration and are destroyed, so that a 
larger or smaller proportion of the constituents of the 
walls of the vessel perishes; and, in the next place, a 
second series of changes, in which we can distinguish @ 
stage of irritation preceding the fatty metamorphosis, 
comparable to the stage of swelling, cloudiness, and en- 
largement which we see in other inflamed parts. I have 
therefore felt no hesitation in siding with the old view in 
this matter, and in admitting an inflammation of the in- 
ner arterial coat to be the starting point of the so-called 
atheromatous degeneration ; and I have moreover en- 

















THE ATHEROMATOUS PROCESS. ; 397 


deavoured to show that this kind of inflammatory affec- 
tion of the arterial coat, is in point of fact exactly the 
same as what is universally termed endocarditis, when it 
occurs in the parietes of the heart. There is no other 
difference between the two processes than that the one 
more frequently runs an acute, the other a chronic, 
course. 

By the establishment of this distinction between the 
different processes which occur in the arteries, the differ- 
ence of the course they pursue is at once accounted for. 
Last time I laid an artery before you, on the inner sur- 
face of which you saw little whitish patches, which were 
due to simple fatty transformation. To-day you see very 
extensive patches in the aorta, in which the atheromatous 
change has taken place. But, as is wont to be the case 
in changes of this kind, in addition to the specific trans- 
formation attendant upon the chronic inflammatory pro- 
cesses going on in the deeper parts, you find on the sur- 
face also a simply fatty change, so that we have the two 
processes occurring together. If now we examine athe- 
romasia a little more minutely, for example in the aorta, 
where the process is the most common, the first thing we 
see present itself at the spot where the irritation has taken 
place, isa swelling of larger or smaller size and not unfre- 
quently so large as to form a really hump-like projection 
(Buckel) above the level of the internal surface. These 
projections are distinguished from the neighbouring parts 
by their translucent, cornea-like appearance. In their 
deeper parts they look more opaque. When the change 
has lasted for a certain time, the first further metamor- 
phoses do not show themselves at the surface, but just 
where the internal comes into contact with the middle 
coat as has been very well described by the old writers. 
How often have they distinctly contended that the 
internal coat could be stripped off over the affected spot! 


398 LECTURE XVI. 


Hence arose the description of Haller, that the pultace- 
ous, atheromatous mass lay in a close cavity, as it were 
a little cystic tumour between the internal and middle 
coat. The only mistake was, that the tumour was re- 


garded as a distinct body separable from the coats of the. 


vessels. It is rather the internal coat itself which without 
any well defined limits passes into a state of degeneration 
within the prominent spot. The farther this degeneration 
advances, the more distinctly does an enclosed collec- 
tion arise out of the destruction of the deepest layers of 
the internal coat ; and at last it may be that the swelling 
fluctuates, and that upon cutting into it the pultaceous 
matter is evacuated, like the pus, when an abscess is cut 
into. Now if the mass be examined which is present at 


Fig. 116. 








Fig. 116. Vertical section through the walls of the aorta at a sclerotic part in 
which atheromatous matter is already in the course of formation. m m’. Middle 
coat, 7 2’ 2”, internal coat. Ats the highest point of the sclerotic part where it pro- 
jects into the cavity of the vessel, i the innermost layer of the internal coat running 
over the whole dépot, ¢’ the proliferating, sclerosing layer, preparing for fatty dege- 
neration, 2” the layer immediately adjoining the middle coat which has already un- 
dergone fatty degeneration, and at e, e, is in process of direct softening. 














ATHEROMATOUS DEPOSITS IN ARTERIES. 399 


the close of this process, numerous plates of cholestea- 
rine are seen, which display themselves even to the naked 
eye as glistening lamelle ; large rhombic tablets, which 
lie together in large numbers, side by side, or covering 
one another, and altogether produce a glittering reflec- 
tion. In addition to these plates, we find under the 
microscope black-looking granule-globules, in which the 
individual fat-granules are at first very minute. These 
globules are often present in 

very large quantity ; some of Wigs 447, 

them are seen, breaking up, 

and falling to pieces, parti- 

cles of them swimming about, 

as in milk. Besides these 

there are amorphous frag- . 
ments of tissue of larger or 

smaller size which still cohere, 

and are rather due to the soft- 

ening of the rest of the sub- 

stance of the tissue which has 

not undergone fatty degeneration ; and in them heaps 
of granules are here and there imbedded. Jt is these 
three constituents together, the cholestearine, the granule- 
cells and fat-granules, and finally the large lumps of half- 
softened substance, which give the atheromatous matter its 
pultaceous character, and really produce a certain degree 
of resemblance to the contents of a pultaceous [sebace- 
ous, epidermic] cyst (Griitzbeutel) of the skin. With 
regard to the cholestearine, it is by no means a specific 
product, appertaining to this kind of fatty transforma- 

















Fig. 117. The pultaceous atheromatous matter from a patch in the aorta. aa’. Fluid 
fat,the product of the fatty metamorphosis of the cells of the internal coat (a), 
which become transformed into granule-globules (w’ a’), then disintegrate and set 
free large and small drops of oil (fatty débris). 6. Amorphous, granularly-wrinkled 
flakes of tissue softened and swollen by imbibition. ¢, e’. Crystals of cholestea- 
rine; ¢ large rhombic plates; c¢, ¢’ fine rhombic needles, 3800 diameters. 


- 400 LECTURE XVI. 


tion alone. On the contrary, we see in every case, 
where fatty products remain stagnant for a considerable 
time within a closed cavity in which but little inter- 
change of matter can go on, that the fat sets free cho- 
lestearine. All the masses of fat which we meet with . 
in the body contain a certain quantity of cholestearine 
in combination. As to whether the cholestearine which 
is set free had already previously existed, or whether a 
real new formation of it takes place in the parts, not 
a word can as yet be said, inasmuch as no chemical 
fact has, it is well known, been made out, which throws 
any light upon the manner in which the formation of 
cholestearine is effected, or upon the substances, out of 
which cholestearine may be formed. This much, how- 
ever, we must hold fast, that cholestearine is a product 
set free at a late period from stagnating, and, particularly, 
from fatty matters. 

I may take this opportunity to mention the reaction 
of cholestearine with iodine and sulphuric acid, which 
has recently become important, and is similar to that 
which we have already (p. 31) considered when speak- 
ing of the cellulose of plants. When, namely, iodine 
alone is added to cholestearine, no change is seen any 
more than in cellulose, under similar circumstances ; 
but when, on the other hand, sulphuric acid is applied 
to the iodized mass of cholestearine, its plates become 
coloured and assume, particularly at first, a brilliant 
indigo-blue tint, which gradually passes into a yellowish 
brown, until the cholestearine is converted into a brown- 
ish drop. Sulphuric acid alone produces a fatty-looking 
substance which is neither cholestearine, nor any special 
combination of cholestearine and sulphuric acid, but a 
product of the decomposition of the former. Sulphuric 
acid alone also produces very beautiful phenomena of 
colour with cholestearine. 


ent a CL LL OO - 

















‘ FORMATION OF ATHEROMA IN ARTERIES. 401 


If now, gentlemen, we trace the development of the 
atheromatous condition a little further back, we come— 
anteriorly to the period when the pultaceous matter is 
found in the seat of the atheroma—across a stage, 
where nothing more is found than fatty degeneration in 
its ordinary form of granule-cells, and we distinctly con- 
vince ourselves, that the process in this stage absolutely 
differs in no respect from that which -in the case of the 
heart and kidney we have just declared to constitute the 
stage of fatty metamorphosis. At this period, imme- 
diately before the formation of the dépdt, the state of 
matters, as seen with a high power, is about as follows. 
On making a section we see the fatty cells which are 
interspersed through the tissue becoming larger towards 
the middle and lying more closely together, but gene- 


Fie. 118. 


[pez 
— 


: = a = 
Presa 


—~ 
—= 





rally bearing the form of cells; but, as we proceed 
from within outwards they become smaller and less 
numerous. All these cells are filled with small, fatty 
granules which strongly reflect the light. Hereby is 
produced what looks to the eye in a section like a whitish 
spot. Between these fatty corpuscles runs a meshed 


Fig. 118. Vertical section from a sclerotic plate in the aorta (internal coat, inner 
surface) in process of fatty degeneration ; 7, the innermost part of the coat with 
round nuclei, isolated, and in groups of several (divided). h. The layer of en- 
larging cells; networks are seen with spindle-shaped cells which enclose sections 
of cells resembling those of cartilage. p. Proliferating layer; division of the 
nuclei and cells. a, a’. The layer which is becoming atheromatous; a, the com- 
mencement of the process, a’, the advanced stage of fatty degeneration. 300 
diameters. 


402 LECTURE XVI. 


basis-substance, the really fibrous stroma of the internal 
coat, which we plainly see continued towards the exte- 
rior into the normal internal coat. This fact, that we 
are able to acquire the direct conviction that the fibrous 
layer which lies over the dépdt, is continued into the 
fibrous layer of the neighbouring normal portions of the 
internal coat, is one of especial value in the interpretation 
of these processes. In this manner the view which was 
for a considerable time defended by Rokitansky also, 
that the affection consists in a deposit upon the ternal 
coat, is refuted. In a vertical section it is distinctly 
seen that the most external layers run in a curve over 
the whole swelling and return into the internal coat, and 
the old writers were quite right when they said—speak- 
ing of a stage in which the formation of the athero- 
matous dépdt had already made considerable progress— 
that the internal coat over the whole of the dépdt could 
be stripped off in a piece. On the other hand, however, 
we can convince ourselves, that the inferior layers of 
the internal coat run directly into the dépdt, and that 
their continuity has been broken by their degeneration, 
so that we have not to deal: either with an interjacent 
deposit (between the internal and middle coat), as the 
old writers supposed, but the whole of what we have 
before us is degenerated internal coat. 

In some particularly violent cases the softening mani- 
fests itself even in the arteries not as the consequence 
of a really fatty process, but as a direct product of 
inflammation. Whilst at the circumference a fatty 
softening takes place, in the centre of the seat of change 
a yellowish cloudy appearance is seen to arise, where- 
upon the substance almost immediately softens and dis- 
integrates, and a mass of coarse, crumbling fragments is 
found (Fig. 116, e, e) which fills the centre of the athe- 
romatous dépdt. 


| 











SCLEROSIS AND OSSIFICATION OF ARTERIES. 403 


In the last place, it is a question where the seat of 
the fatty degeneration really is. Here too again (as in 
the cornea) it may be imagined that the fat is deposited in 
spaces intervening between the lamella ; and even now 
there are still a small number of histologists who will 
not admit, that connective tissue contains only cells, 
and no empty spaces. But if a section through one of 
these (atheromatous) patches be examined from below 
upwards, it is seen that the same structure which pre- 
sents itself in the fatty parts, shows itself also in the 
merely horny or half cartilaginous layers. Bands of 
fibres, in the intersections of which small lenticular 
cavities appear, are found there as they are also in the 
normal condition of the internal coat; but in the cavities 
and in the bands of fibres lie cellular elements (Fig. 
118). The enlargement which the part undergoes in 
consequence of the process and which we call sclerosis, 
depends upon this; the cellular elements of the coat 
increase in size and a multiplication of their nuclei 
takes place, so that spaces are not unfrequently found 
in which whole heaps of nuclei are lying. This is the. 
mode in which the process sets in. In many cases 
division occurs in the cells, and a great -number of 
young cells are met with. These afterwards become the 
seat of the fatty degeneration (Fig. 118, @, a’), and then 
really perish. Thus we have here an active process, — 
which really produces new tissues, but then hurries on 
to destruction in consequence of its own development. 
But one who knows that the fatty degeneration is here 
only a termination, and that the process is really a 
formative one, inasmuch as it begins with a proliferation 
—he can readily imagine the possibility of another ter- 
mination, namely osszfication.. For here we have really 
to do with an ossification, and not merely, as has re- 
cently been maintained, with a mere calcification ; the 


oa 


a 


404 LECTURE XVI. 


plates, which pervade the inner wall of the vessel, are 
real plates of bone. Since they form out of the same 
sclerotic substance from which in other cases the fatty 
mass arises, and since a real tissue can only arise out of 
a pre-existing one, it follows of course that, when the 
process terminates in fatty metamorphosis, we cannot 
assume this to consist in a simple dissemination of fatty 
particles which has taken place in whatever interspaces 
we like to fix upon. 

The essential difference which exists in a large vessel, 
as for example, the aorta, between this process [athe- 
roma] and simple fatty degeneration is therefore this, 
that in the latter a very slight swelling arises on the 
surface of the internal coat, a swelling, which at once 
disappears if the superficial layers be removed by a 
horizontal section, and beneath which there still remains 
a portion of the coat unaltered. In the other case, on 
the contrary, we have in the extreme stage a dépdt 
which lies deep beneath the comparatively normal sur- 
face; afterwards bursts, discharges its contents and forms 
the atheromatous ulcer. This commences as a small hole 


in the internal coat, through which the thick, viscous 


contents of’ the atheromatous dépdt are squeezed out 
on to the surface in the form of a plug; gradually 
more and more of these contents is evacuated and 
carried away by the stream of blood, until at last there 
remains a larger or smaller ulcer which may extend as 
far as the middle coat, and indeed not unfrequently 
involves it. We have therefore always to deal with 
serious disease of the vessel leading to just as destruc- 
tive results, as we see in the course of other violent 
inflammatory processes. You need only apply these 
observations to the history of endocarditis, and you will 
have a correct notion of all that goes on there also. 

In the valves of the heart also we find simple fatty 


hb 


: ENDOCARDIAL EXCRESCENCES. 405 


degeneration taking place both at the surface and deep 
beneath it. The process generally pursues its course so 
latently that no disturbance is perceptible during life, 
nor are we able, in the present. state of our knowledge, 
to name any very obvious anatomical change as being 
the subsequent result of it. On the other hand, what 
we call endocarditis, what can be demonstrated to arise 
in the course of rheumatism, and may indubitably ap- 
pear as a sort of equivalent to the rheumatism of the 
peripheral parts, begins with a swelling of the deceased 
spot zzse/f. There is, namely, no exudation, but the 
cellular elements take up a greater quantity of material, 
and the spot becomes uneven and rugged. Then we 
see, when. the process runs its course somewhat slowly, 


Fie. 119 





Re 
\\ 
SE 


x 


ZS 





Cs 






either that an excrescence, a condyloma arises, or that 
the swelling assumes a more mammillated form, and af- 
terwards becomes the seat of a calcification which may 
produce real bone. If the process runs a more acute 
course, the result is either fatty degeneration or soften- 
ing. The latter gives rise to the ulcerative forms, in 
which the valves crumble to pieces, drop off, and em- 


Fig. 119. Condylomatous excrescences of the mitral valve; simple, granular 
swellings (granulations) and larger prominences (vegetations), some villous, others 
branched and putting forth secondary buds; in all elastic fibres running upwards. 
70 diameters. 


406 LECTURE XVI. 


bolical deposits are produced in remote parts (Fig. 73, 
p. 242).* 

Only iv this manner, by observing, namely, the earli- 
est stages of the changes, is it possible to form certain 
and practically useful opinions with regard to pathologi- 
cal processes. Never ought one, basing one’s opinion 
‘apon the difference of the processes in a clinical point 
of view, to allow oneself to be induced to regard their 
ultimate products as necessarily different. The most 
violent inflammatory processes which run their course 
in quite a short time, may have the same terminations 
as those which, in other cases, are brought about more 
slowly. 

It is not my intention to go through the series of the 
different passive disturbances which may possibly arise 
in the later stages of irritative conditions, in detail. 
Else we should be able to discover analogous instances 
in the history of nearly all degenerative atrophies. In 
all cases we must discriminate between the conditions in 
which a part becomes directly the seat of such a retro- 
gerade metamorphosis, and those in which it previously 
underwent an active change. 

The description which I have given you of the fatty 
processes directly applies to the class of calcifications. 
If it be wished to discriminate between ossification and 
calcification, it is not sufficient to keep the ultimate re- 
sult in one’s eye. <A part does not become true bone, 


* This theory of the detachment of fragments from the valves of the heart, and 
of the consequent secondary occlusions (embolia) was propounded by me, with . 
illustrations from the histories of patients and the results of post-mortem examina- 
tions (Archiv f. path. Anat. und Phys. vol. I., p. 184) as far back as 1847, or five 
years before Dr. Kirkes, to whom the honour of this discovery is still generally 
ascribed in England, published his papers on the subject. My observations con- 
cerning the detachment of the thrombi in the veins were published a year earlier 
than this, viz., in 1846, and I then hinted at the occurrence of the same process in 
the arteries, although I did not give a full account of it until 1847.—From a MS. 
Note by the Author. 











CALCIFICATION AND OSSIFICATION OF ARTERIES. 407 


because it takes up lime into its intercellular substance 


and has stellate cells present in it; it may in spite 
of all this be nothing more than calcified connective 
tissue. When we speak of pathological ossification, we 
always presuppose that the mass which ossifies has been 
called into existence by an active process, an irritation, 
and not that a previously existing tissue assumes the 
form of bone, by absorbing calcareous salts. We have 
therefore calcifications and ossifications in the vessels. 
In ancient times everything was called ossification. 
Many of the more recent observers have denied that it 
ever does occur in vessels. Ossification does however 
really occur, but so does mere calcification, or, as I will 
briefly term it, petrifaction. The latter is compara- 
tively more frequent in the peripheral arteries, so that 
the condition which is generally regarded as a special 
criterion of the atheromatous process and in which the 
radial artery is felt to be hard and calcareous, and the 
femoral or popliteal is perceived to have hard and rigid 
walls, is no proof at all that the process is an atheroma- 
tous one. Very frequently this induration has its seat 
in the middle coat. In this case the calcification really 
invades the muscular elements, so that the fibre-cells 
of the circular-fibre coat are transformed into calcareous 
spindle-shaped bodies. The calcareous matter may in 
these cases also invade the neighbouring parts, but the 
internal coat may possibly remain quite unaltered. This 
is a process therefore, which differs more from what is 
termed the atheromatous process than periostitis from 


_ ostitis. This species of calcification has no necessary 


connection whatever with an inflammation of the artery , 
it occurs most commonly in cases where there is a ten- 
dency to calcifications generally, and. where calcareous 
salts are set free at other points in the economy and cir- 
culate with the juices. This much at least can with cer- 


408 LECTURE XVI. 


tainty be affirmed, that we are as yet acquainted with no 
stage in these changes, which is at allakin to inflammation. 

On the contrary, we see ossification declare itself in 
the internal coat of vessels in precisely the same manner 
as when an osteophyte forms on the surface of bone | 
amidst all the phenomena of inflammation. The oste- 
ophytes of the inner table of the skull and of the cere- 
bral membranes follow the same course of development. 
as the ossifying plates of the internal coat of the aorta 
and even of the veins. They always begin with a pro- 
liferation of the pre-existing connective tissue, whereby 
partial swellings are produced, in which the deposition 
of the calcareous salts does not take place until a late 
period. As soon as this real ossification exists, we 
cannot help regarding the process as one which has 
arisen out of an irritation of the parts, stimulating 
them to new, formative actions; so far therefore it 
comes under our ideas of inflammation, or at least of 
those processes which are extremely nearly allied to in- 
flammation. When a process of this sort is accessible to 
treatment, we have always other indications for practice, 
than in those cases, in which our object is, by the agency 
of stimulating substances, to prevent the occurrence of 
certain passive disturbances which hinder the part from 
discharging its natural functions. 

What I have said will suffice, I think, to make these, 
in my opinion, extremely important distinctions clear to 
you. In the next lecture I will lay before you that one 
among the degenerative processes which is at the present 
moment the least clear, namely the lardaceous or amyloid 
degeneration. 


te Oot Bie AV Bo 


- 


APRIL 17, 1858. 
AMYLOID DEGENERATION. INFLAMMATION. 


Amyloid (lardaceous or waxy) degeneration—Different nature of amyloid sub- 
stances: concentric and laminated amyloid bodies (brain, prostate), and amy- 
loid degeneration properly so-called—Its course—Commencement of the affec- 
tion in the minute arteries—Waxy liver—Cartilage—Dyscrasic (constitutional) 
character of the disease—Intestines—Kidneys: the three forms of Bright’s 
disease (amyloid degeneration, parenchymatous, and interstitial nephritis)— 
Lymphatic glands—Functional disturbances of the affected organs. 

Infammation—The four cardinal symptoms and their predominance in the different 
schools: the thermic and vascular theory ; the neuro-pathologists, exudations 
—Inflammatory stimuli-—Lesion of fanction—Exudation as a consequence of 
the activity of the tissues; mucus and fibrine—Inflammation as a complex 
irritative process—Parenchymatous and exudative (secretory) form. 


I witt to-day, gentlemen, from among the changes 
which must in general be rather ranked with that class 
of degenerations which are attended with a diminution 
of functional power, introduce to your notice one, which 
has recently acquired especial interest, namely that 
which has been by some called the /ardaceous (bacony— 
speckig), by others the wazy, whilst I have given it the 
name of the amyloid, change. The term lardaceous 
change has again come more into use chiefly through 
the instrumentality of the Vienna school. You know 
that the term itself is of tolerably ancient date in medi- 


cine as a denomination for a firm, compact, homogeneous 
409 


410 LECTURE XVII. 


appearance of parts. We find it has been employed for 
centuries, and even in recent times tumours have been 
termed lardaceous. Still the term, lardaceous changes, 
as now used, has but very little to do with these tu- 
mours, and rather refers to things, upon which the old - 
writers, who, I think, were better connoisseurs in bacon 
than our friends in Vienna, would hardly have bestowed 
such aname. The appearance of such organs, namely, 
as in accordance with Viennese ideas, are said to look 
like bacon, bears, according to northern notions, a much 
greater resemblance to wax, and I have therefore now 
for a long time, like the Edinburgh school, made use of 
the term waxy change instead. When we look at a 
liver or lymphatic gland which constitutes a well- 
marked specimen of this condition, what strikes the 
naked eye most, is the translucent, but at the same time, 
dull appearance which the cut-surfaces exhibit; the 
natural colour of the parts is also more or less lost, so 
that a material, at first more of a grey tint, but after- 
wards perfectly colourless, seems to fill the parts. The 
translucent nature of the tissue allows, however, the red 
of the vessels and the natural hue of the neighbouring 
parts to glimmer through, so that the altered spots in 
different organs have rather a yellowish, reddish, or 
brownish tinge ; but this is not a colour belonging to the 
substance deposited. 

The first facts, by the help of which we were enabled 
to determine more accurately the nature of this sub- 
stance which had previously been taken, sometimes for 
a peculiar fatty matter, sometimes for albumen or 
fibrine, sometimes, finally, for a colloid substance, were 
furnished by the application of iodine to animal tissues. 
It will now soon be five years since I first discovered the 
peculiar reaction of the corpora amylacea found in 
the nervous centres with iodine, which I have already 














LAMINATED AMYLOID-BODIES (BRAIN, PROSTATE), 411 


described to you, and since I had my attention directed 
to the extraordinary resemblance which these bodies. 
present to vegetable structures—a resemblance such 
that they have been regarded, now rather as real starch, 
now rather as analogous to cellulose. The next organ 
I came across, although there is no close resemblance in 
external appearance between it and the ependyma, was 
the spleen and indeed a condition of it, in which its 
follicles were wholly converted into this translucent, 
waxy matter (sagoey spleen—Sagomilz). Soon after- 
wards H. Meckel published his well-known observations 
which demonstrated the occurrence .of this substance 
in several places, but especially in the kidneys, the liver 
and the bowels, and we afterwards succeeded in finding 
it in different other parts, in the lymphatic glands, 
throughout the whole of the digestive tract, in the 
mucous membranes of the urinary passages, and finally 
even in the substance of the muscular organs—the heart, 
and the uterus—as well as in the interior of cartilages— 
so that at the present moment there are but few parts 
of the body that we do not know may undergo this pe- 
culiar change. 

If we investigate the matter more closely, it seems 
that two allied, but not identical, substances must be 
distinguished. In the first place we find bodies which 
in their chemical properties are more analogous to real 
vegetable starch, and in form too bear an extraordinary 
resemblance to vegetable starch-granules, inasmuch as 
they constitute more or less round, or oval structures, 
formed by a succession of concentric layers. To this 
class belong, above all, the corpora amylacea of the ner- 
vous system (Fig. 94). Many of the laminated amyloid 


bodies are of very large size; their diameter may be- 


come so considerable, that they may be very distinctly 
recognized with the naked eye. To this category be- 


419 LECTURE XVII. 


long, in particular, a part of the laminated bodies, that 
are found in the prostate of every adult man and under 
certain circumstances accumulate in large quantities, so 
as to form the so-called prostatic concretions ; and also 
rare forms of a similar kind which have been shown by . 
Frederich to occur in several conditions of the lungs. 
These formations vary in size from very small, simple, | 
homogeneous looking. structures up to gigantic bodies, in 
which, when they are regularly formed, we see a suc- 
cession of very numerous layers. Just as the small 
amyloid corpuscles of the nervous system are frequently 
composed of two separate ones and constitute twin 
structures, it very frequently happens here also, that a 
common envelope encloses separate centres (Fig. 120, 
d, e). Nay, in isolated cases this goes on to such an 
extent, that whole heaps of smaller bodies are held 
together by larger common layers. These very large 


Hig. 120; 





Fig. 120. Laminated prostatic amyloid bodies (concretions); a, oblong, pale 
homogeneous corpuscle, with a nucleus-like body. 6. A larger, laminated corpuscle 
with pale centre. c. A still larger corpuscle with several layers and a coloured 
centre. d, e. Bodies with two and three centres, in d of a deeper colour. /. Large 
concretion with a dark-brown, large centre. Magnified 300 diameters. 








THE TRUE AMYLOID DEGENERATION. 413 


though certainly more rare, forms may attain a diameter 
of two lines, so that they can easily be isolated from the 
tissue in which they lie, and be subjected to examination 
even with the naked eye. There seems to be scarcely 
any doubt, but that in these cases a substance is set 
free, which gradually adheres to the outside of pre-ex- 
isting bodies all round, and that therefore we have not 
here to deal with the degeneration of a definite tissue, 
but with a kind of separation and precipitation, such as 
we see occur in the case of other concretions from 
fluids. It may, with some probability be concluded, 
that the prostate, through the dissolution of its elements, 
furnishes a fluid which, by the gradual formation of de- 
posits, produces these particular forms. 

Now the peculiarity of these structures is, that by the 
simple action of iodine they very frequently assume just 
as blue a colour as vegetable starch does. According as 
the substance is more or less pure, its colour changes, so 
that when, for example, there is much albuminous matter 
mixed up with it, it becomes green instead of blue ; for 
the nitrogenous substance is rendered yellow by iodine, 
and the amyloid blue, so that the whole effect produced 
is green. The greater the quantity of nitrogenous mat- 
ser, the browner does the colour become, and not unfre- 
quently do we find, side by side in the prostate, concre- 
tions, which, after the application of the iodine, present 
the most varied colours. So far these formations are 
distinguished from those little. amylaceous .corpuscles 
of the nervous system, which, one and all, assume a blue 
or bluish grey colour on the addition of iodine. It must 
also be remarked, that many prostatic bodies, though 
quite analogous in their structure, only become yellow or 
brown upon the addition of iodine, and consequently dif- 
fer in chemical constitution. 


414 LECTURE XVII. 


Essentially different from this separation of starch-like 
matter, which lies detween the elements, are the degene- 
rations of the tissues themselves, in which all their con- 
stituents (parenchyma and interstitial tissue), as such, 
become directly filled with a substance also of an amy- 
loid nature, and are gradually infiltrated with it just as — 
tissues become infiltrated with lime in calcification. No 
two things can be more justly compared than calcification 
and the amyloid change (lignification). This (amyloid) 
substance, which produces the real degeneration of the 
tissue, exhibits the peculiarity, that it never becomes blue 
under the influence of iodine alone. At least no case is 
as yet known, in which the substance has yielded this 
colour with iodine in the parenchyma of tissues. On the 
contrary, a peculiar yellowish red colour is seen to arise, 
which it is true in many cases has a slight tinge of red- 
dish violet, so that a certain approximation is manifested 
to the blue of real starchy matter. On the other hand, it 
displays pretty regularly a real, either perfectly blue, or 
violet colour, when the application of iodine is followed 
by the very cautious addition of sulphuric acid. <A certain 
degree of practice indeed is requisite ; the exact propor- 
tion must be hit upon; inasmuch as the sulphuric acid 
generally destroys the substance very quickly, and either 
very indistinct colorations are obtained, or the colour 
manifests itself only for a moment, and then immediately 
disappears again. Thus this substance is less nearly allied 
to starch properly so-called and more akin to cellulose, as 
I have already described it (p. 31). But from cellulose 
again itis also distinguished by the fact of its becoming 
coloured upon the application of pure solution of iodine, 
whilst real cellulose is not at all coloured by iodine alone. 
Cellulose behaves precisely like cholestearine which re- 
mains colourless when treated with iodine, but on the 








AMYLOID DEGENERATION OF MINUTE ARTERIES. 415 


other hand assumes a-blue, or under certain circum- 
stances a red, or orange colour upon the addition of 
iodine and sulphuric acid (p. 400). 

Owing to this multiplicity of reactions it is really still 
very difficult to say with certainty to what class the sub- 
stance belongs. Meckel has followed up the idea with 
great care, that we have to deal with a kind of fat which 
is more or less identical with cholestearine ; but we are as 
yet unacquainted with any kind of fat which combines in 
itself the three qualities of becoming coloured upon the 
addition of iodine alone, of remaining colourless upon the 
addition of sulphuric acid alone, and of assuming a blue 
colour when acted upon by iodine and. sulphuric acid. 
Besides the substance itself does not in any way behave 
like a fatty matter ; it does not possess the solubility 
which characterizes fat ; and in particular no substance 
can be obtained from these parts by extraction with 
alcohol and ether, which possesses the peculiarities of the 
original one. According to all this there is rather a 
correspondence with vegetable forms, and the view may 
still be maintained, that we have here to deal with a 
process comparable to that which we see set in during 
the development of a plant, when the simple cell 
becomes invested with capsular layers, and gradually 
grows woody.* 


* The analyses of amyloid spleens recently made by Kekule and Carl Schmidt 
have yielded such a large proportion of Nitrogen, that both these chemists have 
come to the conclusion that the amyloid substance is of an albuminous nature. We 
know, however, from experience, that the results furnished by these analyses of 
whole organs are very little to be depended upon, so little indeed, that no chemist 
was ever able to infer from any analyses he had made of the liver, that it was rich 
in Glycogen. Only when we have discovered the means of isolating the amyloid 
substance, shall we be able to come to any definite conclusion with regard to its 
nature. 

To Schmidt’s analyses of the corpora amylacea of the brain we cannot attach the 
slightest importance, because his statements concerning them were founded upon 
an error. He says, namely, he selected for his analyses a choroid plexus (from a 
human brain) rich in corpora amylacea. But corpora amylacea are never found in 


416 LECTURE XVII. 


These changes can be best followed in those structures 
which must on the whole be regarded as the most fre- 
quent and the earliest seat of this change, namely the 
smallest arteries. These first undergo the transformation, 
and only after the constitution of their walls has become 
changed, is the infiltration wont to extend to the sur- 
rounding parenchyma, until at last the whole district of 
tissue to which the artery leads has experienced the 
change. If in an amyloid spleen we trace one of these 
small arteries, whilst it breaks up into so-called penicillus, 
we see how its wall, in itself already a thick one, becomes 
thicker in proportion as the change advances, and how 
at the same time the calibre of the vessel becomes con- 


Fig. 131, 





siderably diminished. This accounts for the circum- 
stance, that all organs which experience the amyloid 
change in a considerable degree, look extremely pale ; an 


Fig. 121. Amyloid degeneration of a small artery from the submucous tissue of 
the intestine, with its trunk still intact. 300 diameters. 


large numbers in these plexuses—indeed it seems to me doubtful whether they are 
ever formed there. The concentric corpuscles which Schmidt examined were 
therefore probably those sabulous bodies (Sandkérper—acervulus cerebri, brain- 
sand) which are nearly always present in the choroid plexuses and so greatly re- 
semble the corpora amylacea in structure, that they were actually taken by Remac 
to be such. Schmidt, thinking he had the same substance before him in the spleen, 
published his two analyses with the idea that he was thereby furnishing a doubly 


strong proof of the albuminou% nature of this animal amyloid substance.—From a 
MS. Note by the Author. 





AMYLOID DEGENERATION OF THE LIVER. 417 


ischemia of the parts is produced by the obstruction 
which the narrowed vessels oppose to the influx of blood. 
If now we examine in which of the histological elements 
of the vessels the substance is first found, it seems to be 
a constantly seated in the little muscles of the circu- 
ar-fibre coat. First of all the place of every fibre-cell is 
occupied by a compact, homogeneous body, in which the 
centre of the nucleus at first still appears as a hole, but 
gradually every trace of a cellular structure is lost, so 
that at last a kind of spindle-shaped flake (Scholle) re- 
mains, in which neither membrane, nucleus nor contents 
can be distinguished. In the calcification of small 
arteries exactly the same process takes place ; the mat- 
vidual fibre-cells of the middle coat take up calcareous 
salts, at first in a granular, afterwards in a homogeneous 
form, until they are at last transformed into homogeneous- 
looking calcareous bodies, of a spindle-shaped form, which 
coalesce and produce plates of a considerable size. In like 
manner the amyloid substance pervades whole tracts of 
tissue, and the walls of the artery are transformed into a 
mass at last nearly completely homogeneous, compact, 
shining with reflected light and colourless, which not 
only does not possess the hardness of calcified parts, but 
on the contrary exhibits a high degree of friability. 

Now when a change of this nature has advanced to a 
certain height, an analogous change takes place also in 
the parenchyma of the organs. This can nowhere be so 
distinctly traced as in the fiver. Here it sometimes 
happens, that we meet with stages, where nothing else 
in the whole organ is altered, excepting the minute 
branches of the hepatic artery. On making fine sections 
through the liver, carefully washing them and applying 
iodine, we sometimes see, even with the naked eye, the 
small iodine-red lines and points which correspond 


to the cut branches of the hepatic artery. In a later 
27 


A18 LECTURE XVIL. 


stage, however, it is essentially the hepatic cells which 
are affected by the change; and indeed, what is again 
very characteristic, just those hepatic cells, between 
which lie the capillary ramifications of the hepatic ar- 
tery. If namely we picture to ourselves a single acinus 
of the liver, we can, in accordance with the pathologi- 
cal changes which may often be recognized even with 
the naked eye, distinguish three different zones within 
each acinus (Fig. 110). The most external part, which 
lies next to the branches of the portal vein, is the chief 
seat of fatty infiltration ; the intermediate part, which re- 
ceives the capillary terminations of the hepatic artery, 
belongs to the amyloid degeneration, and the central 
part of the acinus around the vena hepatica is the most 
common seat of pigmentary infiltration. Even with 
the naked eye the pale colourless, translucent and re- 
sistant zone of the waxy or amyloid change is sometimes 
recognized between the most external yellowish white, 
and the most internal yellowish, or greyish brown, layer. 

If a single hepatic cell be watched, its previous granu- 
lar contents, which give every hepatic cell a slightly 
cloudy appearance, are seen gradually to become homo- 
geneous ; the nucleus and cell-wall gradually disappear, 
and at last a stage sets in in which nothing move can 
be perceived than an absolutely homogeneous, slightly 
shining body, if you will, a simple flake (Scholle). In 
this manner the whole of the hepatic cells in the zone 
I have described are sometimes converted into amyloid 
flakes, and if the process attains a very high pitch, the 
change at last even oversteps this zone, and it may hap- 
pen, that nearly the whole substance of the acinus is 
transformed into an amyloid mass. Thus out of the 
hepatic cells there is at last produced in these cases a 
kind of corpora amylacea, only they are not laminated 
like those we have already spoken of, but form uniform, 


ole oF «> 
ae 


DYSCRASIC NATURE OF THE AMYLOID DEGENERATION. 419 


homogeneous bodies, in which no internal division, no 


indication of the peculiar course of their formation can 


be recognized. 

If we take all these facts together, it appears pretty 
probable, that we have here to deal with a gradual infil- 
tration of the parts with a substance which has been 
conveyed to them from without. This is a. view which 


. derives essential support from the fact, that nearly 


always when this change declares itself, a considerable 
number of organs are affected, and that the process is 
not confined to a single spot, but that many places in 
the body are simultaneously affected. Hereby the 
whole process really acquires an essentially dyscrasic 
appearance. The only place, where, until now at least, 
an entirely independent development of this change has 
been observed by me, and where it may shetefare with 
some degree of probability be assumed that the forma- 
tion is autochthonous and not imported from without, 
is permanent cartilage. The cartilages, particularly in 
people somewhat advanced in life, assume in various 
places—as for example, the sterno-clavicular articula- 
tions, the symphyses of the pelvis, and the interverte- 
bral cartilages—a peculiarly pale-yellowish hue, and 
then we may be tolerably certain, that if we try the 
iodine test with them, we shall obtain ‘the peculiar 
coloration. These colours are not seen so much in the 
cartilage-cells as in the intercellular substance, and as 
eases of the sort do not occur simultaneously with amy- 
loid degeneration of large internal organs, but quite in- 
dependently, in individuals, who in the rest of their body 
manifest nothing of the kind—it seems that we really 
have here to deal with a direct transformation, and not 
with any importation from without. 

But in vain have I hitherto endeavoured to detect any 
definite change in the blood, from which the inference 


490 LECTURE XVII. 


might be drawn, that this was really the source of the 
deposits. There exists as yet but one single observa- 
tion, that points to the presence of analogous bodies in 
the blood, and this is so strange an one, that we can 
scarcely attempt to ground an explanation of the pro- 
cess upon it. A physician of Toronto in Canada had 


namely, in compliance with the wish of a patient suffer- - 


ing from epilepsy, examined his blood and discovered in 
it peculiar, pale bodies. When then he read of my ob- 
servations with regard to the coloration of the corpora 
amylacea of the brain by iodine, his patient recurred to 
his mind, and, I think after the lapse of five years, he 
again took blood from him, and again found the bodies, 
which are really said to have exhibited the reaction. 
In opposition to this observation, it is strange that 
nobody else has ever seen anything of the kind, and 
as an extremely persistent dyscrasia must here have 
been in operation, we should scarcely be justified in 
drawing conclusions from this observation, with regard 
to the cases we are considering, where the disease at- 
tains its height in a much shorter time, and we have in 
the blood at least been able to detect nothing of the 
kind. Moreover great doubts must be entertained with 
respect to the accuracy of the observation. Starch- 
granules may very easily find their way into different 
microscopical objects, so that (with all due respect for 
the observer) as long as matter turns upon a solitary 
observation, it must be admitted to be possible that 
there was perhaps an error.* J am as yet much more 
inclined to admit, that the blood in this disease under- 


* Dr. Carter of Edinburgh, and after him, M. Luys of Paris, fell into a similar 
error, when they imagined they were in a condition to prove that an excretion of 
starch took place through the skin. M. Rouget (Journal de Physiologie par 
Brown-Séquard, Tom. ii., p. 85) has shown that this starch is derived from external 
sources, from articles of food, and that its presence upon the skin therefore is 
merely accidental.— From a MS. Note by the Author. 








DYSCRASIC NATURE OF THE AMYLOID DEGENERATION, 49] 


goes a chemical alteration in its fluid constituents, than that 
it contains the pathological substances ina material form. . 

At all events it is unquestionable, that the amyloid 
change even now holds a very high place among patho- 
logical processes. The inevitable result of the affection 
is, that the parts which are the seat of it, become totally 
. incapable of discharging their special functions ; that, 
for example, gland cells which are changed in this man- 
ner, are no longer in a condition to perform their special 
glandular functions, and that vessels can no longer 
subserve the nutrition of the tissues, or the secretion 
of the fluids, the duties they had been in the habit of 
performing. 

These considerations afford a ready explanation of the 
circumstance that clinical disturbances so regularly con- 
cur with these anatomical ones. We find, on the one 
hand, well-marked conditions of cachexia, and on the 
other, with extreme frequency, dropsy with the whole 
complex group of changes, which are usually included in 
the idea we form of Bright’s disease. In nearly every 
instance, in which the amyloid affection reaches an ad- 
vanced stage, the patients are in a state of great maras- 
mus. There are cases where the whole extent of the 
digestive tract from the buccal cavity to the anus does 
not contain a single minute artery, which is not affected 
with this disease, and wherein every part of the ceso- 
phagus, stomach, small and large intestines, the small 
arteries of its mucous membrane are found changed in 
this way. | 

Now this state of things is very apt to escape obser- 
vation, because this kind of metamorphosis, which 
exercises such a decided influence upon the functions 
of the intestines (causing deficiency of absorption, an@ 
tendency to diarrhoea), produces scarcely any effect. per- 
ceptible to the naked eye. The intestines are pale and 


499, LECTURE XVII. 


have a grey, translucent, sometimes slightly wax-like 
appearance ; but this, however, is so little characteristic, | 
that no inference can with certainty be drawn from it 
with regard to the internal changes, and the only possi- 
bility of determining the point, when one has no mi- 
croscope at hand, consists in the direct application of the 
test. One need only brush a little iodine upon the 
surface, and a number of densely aggregated, yellow- 
ish- or brownish-red spots are soon seen to start up, 
whilst the interjacent mucous membrane merely looks 
yellow. These red points are the villi of the intestine, 
and if one of them be placed under the microscope, the 
walls of the small arteries and even of the capillaries, 
which ramify in them, and sometimes also the parenchy- 
ma, are seen to be coloured iodine-red. 

The most important disturbances of this kind with 
which we are as yet acquainted, are those which arise in 
the kidney. <A large proportion of the cases of Bright’s 
disease, especially of the chronic ones, are assignable to 
this change, and must therefore be separated from many 
other similar forms as constituting a special, altogether 
peculiar affection. Kidneys affected in this way were 
called in Vienna, at a time when the chemical reaction 
was not yet known, lardaceous kidneys (Specknieren). 
I must however again remark that it is impossible to 
distinguish immediately with the naked eye, whether 
this particular change has taken place or not, and that a 
part of the so-called lardaceous kidneys exhibit nothing 
more than a kind of induration. Not until iodine has 
been employed can a diagnosis be readily made. If a 
solution of iodine be applied to a quite ansemic cortex, 
a number of red points usually first appear which cor- 
respond to the glomeruli, and sometines fine streaks also, 
which are the afferent arteries ; and next to this, when 
the disease is very severe, red parallel lines are also 


AMYLOID DEGENERATION OF THE KIDNEYS. . 493 


seen within the medullary cones, lying very close to one 
another. These are all arteries. The affection of the 
arteries becomes sometimes so severe, that, after the 
application of the test, a clear view of the whole course 
of the vessels is obtained, as if one had a very complete 
artificial injection before one. But in these very kid- 
neys an injection is hardly practicable. Even the finer 
materials which we employ as injections, are much too 
coarse to be able to pass through the narrowed vessels. 
Upon examining one of these glomeruli microscopically, 
we see that from the point, where the afferent artery 
breaks up, the loops are no longer the fine, delicate 
tubes that they formerly were; on the contrary they 
appear compact and nearly solid. Now as these are 
just the parts which manifestly constitute the real 
points at which the secretion of the fluid portion of the 
urine is effected, we can easily conceive that in such 
cases disturbances in the secretion of urine must arise. 
Unfortunately we have as yet no completely satisfactory 
analyses, but it seems that many cases of albuminu- 
ria, which are attended with a considerable diminution 
in the secretion of urea, are connected with these very 
conditions, and that the excretion becomes more and 
more scanty in proportion as the disease increases in 
intensity.* These cases are very frequently complicated 


* This is what we might expect to take place, wherever we suppose the urea to 
be secreted. If it is secreted by the epithelium, the epithelium must take it up 
out of the blood which circulates in the intertubular capillaries. But if the glo- 
meruli only allow a small quantity of blood to pass through them, a small quantity 
only finds its way into these capillaries, and so but little urea can be taken up and 
excreted. In those cases in which there is an abundant flow of watery urine, the 
water is chiefly derived from the vessels of the medullary substance, in conse- 
quence of the increased (collateral) pressure upon them. Thus the amyloid de- 
generation of the Malpighian bodies and their afferent arteries has much less 
influence upon the excretion of water, than upon that of urea, The peculiar views 
first put forward by the Author concerning the circulation in the medullary sub- 
stance of the kidney, and the common origin (from the same branches of the 
renal artery) of the arteri# recte of the medullary cones (pyramids), and of the 


424 LECTURE XVII. 


with anasarca and with dropsy of the different cavities, 
and may exhibit in the completest manner all the symp- 
toms of Bright’s disease. They differ however es- 
sentially from the simply inflammatory form of Bright’s 
disease, which I designate parenchymatous nephritis, in 
this respect, that in the latter the disease has not so much 
its seat in the glomeruli or the arteries, as in the epithe- 
lium of the kidney, and that the change is often for a 
long time confined to the epithelium, whilst the glome- 
ruli themseives may in such cases still appear unchanged 
when there is scarcely any epithelium remaining in the 
substance of the cortex. From these forms a third 
again must be distinguished, where the interstitial tissue 
is predominantly affected, where thickenings take 
place around the capsules and uriniferous tubules, con- 
strictions and contractions are effected, and thereby 
mechanical obstructions to the current of the blood are 
produced, which must naturally be attended by secre- 
tory changes. 

It is very important that you should discriminate 
between these different varieties which exist in what is 
apparently a single disease, because you will hence see 
how it is that the facts which have been ascertained con- 
cerning the one class cannot forthwith be applied to the 
other classes, and that neither the same physiological 
inferences nor the same therapeutical maxims are equally 
applicable in every one of these several conditions. At 
the same time, however, it must not be overlooked that 
these three different forms by no means always appear 
afferent arteries of the cortex, whereby, in the case of a diminished flow of blood 
through the latter set of vessels, an increased circulation takes place through the 
former—will be found in his Archiv. f. path. Anat. und Phys. vol. xii., p. 8310, and 
investigations confirmatory of them have recently been published by Dr. Beale 
(Arch. of Med., 1859, No. IV, p. 300. According to those (e. g., Bowman) who 
make all the arterial blood pass through the glomeruli, no such collateral rela- 


tionship could exist between the cortex and medulla—From a MS. Note by the 
Author. 


ool 
oa : 


AMYLOID DEGENERATION OF THE LYMPHATIC GLANDS. 495 


unmixed, but that on the contrary frequently two, and 
sometimes all three, of them exist simultaneously in the 
same kidney. : 
Amongst the other preparations which I place before 
you I have, especially on account of its distinctness, chosen 
the amyloid disease of the lymphatic glands. In these 
the state of things is much the same as in the spleen. We 
see on the one hand the small arteries, on the other the 
essential substance of the glands (2. e., the mass of minute 
cells which fill the follicles), undergoing the change. You 
will remember from a previous occasion (p. 208, Fig. 61), 
that there are follicles lying beneath the proper capsule 
of the gland, and that these follicles are made up of a 


Fie. 122. 


Fig. 1238. 





Fig. 122. Amyloid degeneration of a lymphatic gland, from a drawing made by 
Dr. Fripp of Bristol. a, 5, 6. Vessels with greatly thickened, shining, infiltrated 
walls. c. A layer of fat-cells at the circumference of the gland. d, d. Follicles with 
their delicate reticulum and corpora amylacea. 200 diameters. Compare Wirz- 
burger Verhandlungen, Vol. VII, Plate III. 

Fig. 123. Isolated corpora amylacea of different sizes, some of them ruptured, 
from the gland represented in Fig. 122. 350 diameters. 


496 LECTURE XVII. 


delicate network, in which the small cells of the gland are 
heaped up, cells, which seem to have a double duty to 
perform, inasmuch as they discharge their own special 
functions as gland-cells, and at the same time, as we sup- 
pose, serve as the starting-points for the development of © 
blood-corpuscles. The arteries run first in the inter- 
stices of the follicles, and there break up into capillaries 
which form a web round the follicles, and sometimes even 
penetrate into their interior. Now the amyloid disease 
consists on the one hand in a thickening and narrowing of 
these arteries, so that they convey less blood, and on the 
other hand in the conversion of the small cells contained 
in the individual meshes of the follicles into corpora amy- 
lacea, so that afterwards instead of a number of cells in 
every mesh of the follicle, a single large corpus amylaceum 
is met with. Thereby the gland acquires even to the 
naked eye the appearance as if it were sprinkled all over 
with little spots of wax, and when examined microscopi- 
cally, it looks as if the contents of the follicles were a 
pavement of closely set stones. 

~ Concerning the importance of these changes, empiri- 
cally not much can be affirmed ; but, if the contents of 
the follicles are the essential components of a lymphatic 
gland, and if from them proceeds the development of the 
new constituents of the blood, we must, I think, conclude, 
that this disease of the lymphatic glands and the spleen 
(in which the follicles are likewise generally affected), 
must exercise a directly mnjurious influence upon the for- 
‘mation of the blood; and that the effects therefore pro- 
duced by the disease are not remote ones, but that the 
formation of the blood immediately suffers an alteration, 
so that aneemic conditions must ensue. To the stream 
of lymph also an obstruction may arise, and in this way 
again deficiency of absorption, tendency to dropsy, etc., 
be praduced. 











INFLAMMATION. | 497 


If we apply iodine to sections of such glands as these, 
all the diseased parts become coloured red, whilst every 
part that retains its normal structure merely becomes 
yellow. The capsule, which consists of connective tissue, 
the fibrous trabecule between the follicles, the delicate 
intrafollicular network which separates the different cor- 
pora amylacea, and lastly those follicles which contain 
normal cells, remain yellow. Allthe other parts assume 
the iodine-red hue. If we add sulphuric acid, these parts 
become of a dark reddish brown, or violet red—or if one 
hits the mark, pure blue; but if there are still nitro- 
genous particles present, the colour becomes green or 
brownish red. 


Now, gentlemen, that we have established the classifi- 
cation of morbid disturbances generally according to the 
difference of action in the tissues, | think of treating 
more in detail of the process, which the practical physi- 
cian, according to the ordinary mode of speaking, most 
frequently meets with, namely inflammation. 

Our notions of inflammation have undergone an essen- 
tial change in consequence of the observations, of which 
you have now heard a certain part. Whilst until quite 
recently it was the custom to look upon inflammation as 
a real entity, as a process everywhere identical 7m ¢is 
essence, after I made my investigations no alternative 
remained, but to divest the notion of inflammation of all 
that was ontological in it, and no longer to look upon 
the process as one differing in its essence from other 
pathological processes, but only to regard it as one differ- 
ing in its form and course. 

In the descriptions given of inflammation by the old 
writers—as preserved to us in the dogmatical writings of 
Galen—among the four cardinal symptoms (calor, rubor, 
tumor, dolor) heat is, as is well known, the most promi 


498 LECTURE XVII. 


nent, for it is the symptom from which the process has 
acquired its name. Afterwards, in proportion as the 
question of animal heat in general, and of heat in patho- 
logical conditions in particular, withdrew into the back- 
ground, great importance was attached to the redness, 
and thus it happened that even in the last century, at the 
time when mechanical theories were in vogue, when 
especially Boerhaave considered inflammation to consist 
in an obstruction of the vessels, and in the stasis of the 
blood consequent upon it, the notion of inflammation was 
more or less grounded upon supposed conditions of the 
vessels. After the facts of pathological anatomy had 
extended their compass, hypereemia was, especially in 
France, declared to be the necessary and regular starting 
point of inflammation. The exclusiveness, with which 
this view has been maintained even up to our own times, 
was in a great measure an after-effect of Broussais’ views 
which became the prevailing ones in consequence of the 
development of the pathologico-anatomical school. Hy- 
peremia gradually superseded all the other essential 
symptoms. 

A change in the doctrine on a grand scale has really 
only been attempted by the Vienna school, for they too, 
like the French school, grounding their system of patho- 
logy upon pathological anatomy, have put the products 
of inflammation in the place of the symptoms of inflam- 
mation. What, basing their opinion upon their own 
experience, they especially had in view, and sought to 
establish as the essence of inflammation, was the product, 
which, in accordance with traditional notions, was desig- 
nated as one which had necessarily proceeded from the 
vessels—as an exudation. In the old classification of 
symptoms, the swelling, corresponded pretty nearly with 
the exudation of the Vienna school, and it might there- 
fore be said that, as previously, first the heat, and then 














INFLAMMATION, 429 


the redness, had held the first place, so now the swelling 
occupied the foremost rank. It is only in the more 
speculative views of the neuro-pathologists that the pain 
is, as is well known, regarded as the essential and origi- 
nal change in the act of inflammation. 

There can be no doubt, but that of these different posi- 
tions the anatomical doctrine of the Vienna school would 
be the most correct, if it could be demonstrated, that, as 
the language of most of the physicians of the present day 
would lead us to believe, an exudation really does take 
place, in every case of inflammation ; that the swelling is 
essentially occasioned by this exudation ; and especially, 
that this exudation ought to be regarded as a constant 
and typical one, and the quantity of fibrine contained in 
it as a criterion of its inflammatory nature. 

I have already, in the previous lectures, endeavoured 
to show you, in what a considerably restricted sense the 
term exudation must be employed, and how essentially 
the activity of the elements of the tissues themselves is 
concerned in the appearance of matters, which we cer- 
tainly must regard as derived from the vessels and depo- 
sited in the parts affected. A good deal is, as we have 
seen, not so much exudation, as, if I may so express 
myself, an educt from the vessels in consequence of the 
activity of the histological elements themselves. 

Irritation must, I believe, be taken as the starting-point 
in the consideration of inflammation, and it is because 
Broussais and Andral regarded the matter in this light, 
that I consider the views advanced by them to be the 
most correct. We cannot imagine inflammation to take 
place without an irritating stimulus (irritament),* and the 


* The term irritament (Reiz, which, however, sometimes means irritant, stimu- 
lus) is intended to express the change (mechanical or chemical, palpable (anatomi- 
cal) or molecular) which takes place in a tissue in consequence of the action of an 
irritant—a change, therefore, which is of a purely passive nature (lesion), and which 


430 : LECTURE XVIL 


first question is, what conception we are to form of such 
a stimulus. 

We have already seen that the irritation may in gene- 
ral be traced to one of three different sources, accord- 


ing as it is a functional, nutritive or formative irritation 


which has taken place. Now there can be no doubt, 
but that functional stimuli (irritaments) do not play an 
essential part in inflammation, and for the simple reason, 
that—a point upon which all the more recent schools at 
least are agreed—to the four characteristic symptoms 
lesion of function (functio lesa) must be added. 

If there be a disturbance of function in inflammation, 
this presupposes that the inflammatory stimulus (irrita- 
ment) must be of such a nature as to cause changes in 
the composition of the part which render it less capable 
of performing its functions. Nobody would expect a 
muscle which is inflamed, to perform its functions nor- 
mally ; every one supposes that the contractile sub- 
stance of the muscle has thereby experienced certain 
changes. Nobody would expect an inflamed gland-cell 
could secrete normally, but we should look upon the 
disturbance of secretion as a necessary consequence of 
the inflammation. Nobody could expect an inflamed 
ganglion-cell or nerve to discharge its functions, or nor- 
mally to respond to stimuli. The conclusion, therefore, 


(subsequently) provokes changes in the neighbouring parts not directly altered by 
the irritant—the consequence of which is their action or reaction. This condition, 
which is an active one, based upon the physiological powers of the parts, represents 
zrritation in the proper sense of the word, and as the starting-point in every. form 
of inflammation. See Archiv f. path. Anat. und Phys. vol. xiv., p. i. (Reizung und 
Reizbarkeit). 

The matter will perhaps be rendered clearer by the following familiar illustration : 
—Suppose three people were sitting quietly on a bench, and suddenly a stone came 
and injured one of them, the others would be excited, not only by the sudden 
appearance of the stone, but also by the injury done to their companion, to whose 
help they would feel bound to hasten. Here the stone would be the irritant, the 
injury the irritament, the help an expression of the irritation called forth in the 
bystanders.—from a MS. Note by the Author. 








INFLAMMATORY EXUDATION. 431 


that must in accordance with the commonest experience 
be necessarily drawn from all this is, that changes must 
have occurred in the composition of the cellular 
elements altering their natural functional power. 
Such changes, when they occur after the application of 
stimuli which are not powerful enough to destroy the 
parts at onee, or to exhaust their functional power, are 
only possible when the stimuli are either nutritive or 
formative. And in fact this conclusion is confirmed by 
what occurs in inflammation. For now-a-days we find 
the view ig already pretty generally spread, that in inflam- 
mation we have in the main to deal with a change in the 
act of nutrition, nutrition being here indeed regarded 
as embracing the formative and nutritive processes. 

If therefore we speak of an inflammatory stimulus 
(irritament), we cannot properly intend to attach any 
other meaning to it, than that, in consequence of some 
cause or other external to the part which falls into a 
state of irritation, and acting upon it either directly.or 
through the medium of the blood—the composition and 
constitution of this part undergo alterations which at 
the same time alter its relations to the neighbouring 
parts (whether they be blood-vessels or other structures) 
and enable it to attract to itself and absorb from them a 
larger quantity of matter than usual, and to transform 
it according to circumstances. Every form of inflamma- 
tion with which we are acquainted, may be naturally ex- 
plained in this way. With regard to every one, it may be 
assumed that it begins as an inflammation from the mo- 
ment that this increased absorption of matters into the 
tissue takes place, and the further transformation of these 
matters commences. 

This view accords to a certain extent, as you no doubt 
see, with that which has been maintained by the up- 
holders of the vascular theory, according to which the 


439 LECTURE XVII. 


exudation is regarded as an immediate: consequence of 
the hyperemia, and in which it is assumed that inflam- 
mation, when it has once declared itself, is characterized 
by the presence of a substance more or less foreign to 
the natural composition of the part. The only question » 
is whether the hyperzemia really forms the actual com- 
mencement of these processes. 

If inflammation were necessarily dependent upon hy- 
pereemia, you can well imagine that it would be logically 
impossible to speak of inflammations in parts which do 
not stand in an immediate relation to vessels. We could 
not imagine an inflammation taking place at a certain 
distance from a vessel. It would be completely impossi- 
ble to speak of an inflammation of the cornea (excepting 
as occurring at its border); of an inflammation of car- 
tilage (excepting as occurring in the parts immediately 
adjoining the bone); or of an inflammation in the 
internal substance of a tendon. But if we compare the 
processes which present themselves in these parts with 
those which are ordinarily seen in inflamed parts, the 
result is unquestionably that the same inflammatory _ 
processes may occur everywhere alike, and that the 
changes in the vascular parts can in no essential parti- 
cular be distinguished from those which take place in the 
non-vascular ones. 

The term inflammatory (7. e., according to the common 
definition, fibrinous) exudation, has, as you are aware, 
been somewhat loosely applied, inasmuch as it has been 
taken to include different kinds of exudation (fibrinous 
and non-fibrinous) furnished by different processes, upon 
all of which, however, the common name of inflamma- 
tion has been bestowed. When, for example, inflam- 
mations of mucous membranes are spoken of, it is not 
generally supposed, that the mucous membrane will 
furnish a fibrinous exudation. We are indeed ac- 





FIBRINOUS EXUDATIONS. 433 


quainted with mucous membranes, where fibrinous ex- 
udations are of pretty frequent occurrence, for example, 
the mucous membrane of the respiratory organs. But 
we know also that free (superficial) fibrinous exudations 
are scarcely to be met with on the mucous membrane 
of the digestive tract, and that they at most accompany 
the more serious, and especially the gangrenous and 
specific forms. When laryngitis is spoken of, the pre- 
sence of croup is not immediately inferred. In a case 
of cystitis, we do not expect to find the inner surface of 
the bladder covered with a fibrinous layer. In the 
whole series of so-called gastric inflammations we find, 
especially at the commencement of the process, scarcely 
anything more than an abundant secretion of mucus. 
If therefore we still call these catarrhal inflammations, 
inflammations, if we do not wish entirely to cast them 
out of the class of inflammations, we must admit that | 
there may exist a mucous as well as fibrmous exudation 
in inflammations, and that the inflammations with a mu- 
cous exudation form a special category, appertaining to 
certain organs. For, as is well known, we do not find 
them in all the tissues of the body, but nearly exclusively 
on mucous membranes. 

If now you consider the fibrinous exudations a little 
more closely, there can be no doubt at all, but that in 
this point they entirely agree with the mucous ones. 
For we do not meet with fibrinous exudations in all 
parts of the body; we know of no form of exudative 
encephalitis, for example, which furnishes a fibrinous 
exudation. Just as little is there a form of hepatitis 
known, in which fibrinous exudations occur. There is 
indeed an inflammation of the investnmg membrane of 
the liver (perihepatitis), just as there is an inflamma- 
tion of the membrane of the brain, in which fibrine 


may be set free, but nobody has ever met with fibrine in 
28 


A394 LECTURE XVII. 


a case of genuine hepatitis. Just as little is there 
fibrine to be found in the ordinary inflammation of the 
substance of the heart (myo-carditis). 

On the other hand, you must bear in mind that, 


starting with certain preconceived notions, observers’ 


have imagined fibrinous exudations to take place in 
many parts, where they are not really to be seen. If 
because pus has been obtained from a fibrinous exuda- 
tion, it is therefore imagined that, wherever pus shows 
itself, a fibrinous exudation must be regarded as its 
source, no very great power of observation is required 
to convince oneself, that this is an error. Take any 
ulcerated surface you please, wipe off the pus, and col- 
lect what then comes out ; you will either have a serous 
fluid or pus, but you will not see that the surface you 
have wiped becomes covered with a fibrinous layer. If 
we confine ourselves to those parts, where inflammations 
with real, unquestionable fibrinous exudation do occur, 
we have a category nearly as limited as that of the mucous 
inflammations. In such a category the first place is 
occupied by the serous membranes proper, which even 
upon slight inflammatory irritation generally produce 
fibrine ; the second place is filled by certain mucous 
membranes, in which, in a great number of cases, 
fibrinous inflammations unmistakably arise, as an aggra- 
vation out of mucous ones. Ordinary croup does not 
generally at its very outset manifest itself in the form of 
fibrinous croup; at the commencement, at a time when 
the danger may already be very considerable, there is 
often nothing else found than a mucous or muco-purulent 
false membrane. Not until after a certain lapse of time 
does the fibrinous exudation set in, and then it does so 
in such a manner, that we can trace the transitions in 
the same false membrane, and see that a certain portion 
is manifestly mucous, another manifestly fibrine, whilst 








PARENCHYMATOUS AND SECRETORY INFLAMMATION. 435 


in a third part it can no longer be affirmed with cer- 
tainty whether the one or the other is present. Here 
therefore both substances appear as substitutes for one 
another. Where the inflammatory irritation is more 
violent, we see fibrine, where slight, mucus, appear. 
With regard to mucus, however, we know, that it 
does not exist in the blood like fibrine. Although a 
mucous membrane produces incredibly large masses of 
mucus in a short time, they are nevertheless products 
of the membrane itself; the membrane is not infiltrated 
with mucus coming from the blood, but the peculiar 
mucin matter, the principle of mucus, is a product of 
the membrane, and is conveyed to the surface by means 
of the fluid oozing through (transuding) from the blood. 
In the same manner | have also attempted, as I inti- 
mated to you on a former occasion (p. 195), to over- 
throw the opinion, which is wont to be entertained with 
regard to the origin of fibrine. Whilst until now fibrine 
has been regarded as a real transudation from the 
liquor sanguinis, as the outflowing plasma, I have pro- 
posed the explanation, that the fibrine, like the mucus, 
is a local product of those tissues, on and in which it is 
found, and that it is conveyed to the surface in the same 
way as the mucus of the mucous membrane. I then 
showed you, how we have in this way a most ready 
explanation of the fact, that in proportion as, in a given 
tissue, the production of fibrine increases, so also the 
amount of fibrine in the blood increases; and that the 
fibrinous crasis is just as much a product of the local 
disease, as the fibrinous exudation is a local product of 
the local metamorphosis of matter. Never has any one 
—any more than it is possible for him by a change of 
pressure directly to produce mucus from the. blood in 
any place which does not itself produce mucus—been 
able to produce fibrine by any change in the pressure of 


436 LECTURE XVII. 


the blood; what transudes never consists of anything 
but serous fluids. | 

I am accordingly of opinion, that, 7m the sense in which 
it has usually been assumed to exist, there is no inflam- 


matory exudation at all, but that the exudation which 


we meet with, is essentially composed of the material 
which has been generated in the inflamed part itself 
through the change in its condition—and of the trans- 
uded fluid derived from the vessels. If therefore a part 
possesses a great number of vessels, and particularly if 
they are superficial, it will be able to furnish an exuda- 
tion,‘ since the fluid which transudes from the blood con- 
veys the special products of the tissue along with it to 
the surface. If this is not the case, there will be no 
exudation, but the whole process will be limited to the 
occurrence in the real substance of the tissue of the 
special changes which have been induced by the inflam- 
matory stimulus. 

In this manner, two forms of inflammation can be 
separated from one another ; the purely parenchymatous 
inflammation, where the process runs its course in the 
interior of the tissue, without our being able to detect 
the presence of any free fluid which has escaped from the 
blood ; and the secretory (exudative) inflammation (which 
belongs more to the superficial organs) where an increased 
escape of fluid takes place from the blood and conveys 
the peculiar parenchymatous matters along with it to the 
surface of the organs. That there are two different forms 
is clearly shown by the fact that they occur for the most 
part in different organs. There are certain organs which, 
under all circumstances, only suffer from the parenchy- 
matous affection, and others again which in nearly every 
instance exhibit a superficial exudative inflammation. 

The distinction into adhesive and puruleint forms, which 
has generally been made in accordance with the example 





PARENCHYMATOUS AND SECRETORY INFLAMMATION. 437 


of Hunter, has reference to a much later stage in the 
process ; the first point to be considered is always, how 
far the tissues themselves become changed and their pro- 
ducts assume a degenerative character, or how far, through 
the passage of the fluids, the part is again freed from what 
it has generated in itself, and how far thereby the dege- 
neration of the part is avoided. Every parenchymatous 
inflammation has from its outset a tendency to alter the 
histological and functional character of an organ. Lvery 
inflammation with free exudation in general affords a 
certain degree of relief to the part ; it conveys away from 
it a great part of the noxious matters with which it is 
clogged, and the part therefore appears comparatively 
to suffer much less than that which is the seat of a 
parenchymatous disease. 


lee i eee i 


APRIL 21, 1858. 
NORMAL AND PATHOLOGICAL NEW-FORMATION. 


The theory of continuous development in opposition to the blastema- and exuda- 
tion-theory—Connective tissue and its equivalents as the most general germ- 
-store of new formations—Correspondence between embryonic and pathologi- 
cal new formation—Cell-division as the most general starting-point of new 
formations. 

Endogenous formation—Physalides—Brood-cavities. 

Different tendencies of new-formations—Hyperplasia, direct and indirect—Hetero- 
plasia—Pathological formative ceils—Difference in their size and in the time 
required for their full development. 

Description of the development of bone as a model formation—Difference between 
formation and transformation—Fresh and growing, in opposition to macerated, 
bone—Nature of medullary tissue—Growth in length of tubular [long] bones ; 
proliferation of cartilage—Formation of marrow as a transformation of tissue ; 
red and yellow, normal and inflammatory marrow—Osseous tissue, calcified 
cartilage, osteoid tissue—Bone territories: caries, degenerative ostitis—Granu- 
tions in bone—Suppuration of bone—Maturation of pus—Ossification of mar- 
row—Growth of long bones in thickness: structure and proliferation of the 
periosteum. 

Granulations as analogous to the medulla of bones, and as the starting-point of all 
heteroplastic development. 


GrENTLEMEN,—I propose to-day, in illustration of /or- 
mative irritation, to portray to you the most import- 
ant features in the history of pathological new-forma- 
tions, for a knowledge of these will throw light upon a 
series of events which present themselves both in the 
more complicated formation of tumours, and in the 


more simple inflammatory irritative processes. That I 
438 





TYPHOUS MATTER. THE CONNECTIVE-TISSUES. 439 


at- present entirely reject the blastema doctrine in its 
original form, you have no doubt already gathered from 
the previous lectures. In its place I have put the very 
simple doctrine of the continuous development of tissues 
out of one another. The chief point therefore in indi- 
vidual cases is to determine the particular manner in 
which the various tissues arise, and by means of definite 
examples to make oneself acquainted with all the 
different directions which it is possible this development 
may follow. 

My first observations, in consequence of which I began 
to entertain doubts with respect to the prevailing blaste- 
ma and exudation doctrine—as to how far namely, new- 
formations could be derived from this souree—date from 
researches of mine on ¢ubercle.* I found namely that a 
series of tubercular deposits in different organs, espe- 
cially in the lymphatic glands, the membranes of the 
brain and the lungs, never at any time exhibited a 
discernible exudation, but always, during the whole 
course of their development, presented organized ele- 
ments, without its ever being possible to observe either 
in them, or before they existed, any stage in which 
amorphous, shapeless matter was present. As long as 
eight years ago I discerned that the development which 
takes place in the lymphatic glands upon the occurrence 
of the well-known scrofulous changes, begins in such a 
way, that the first conditions met with entirely corres- 
pond to those which in other instances are designated 
by the name of hypertrophy; for nuclei and cells are 
found in great abundance, though they afterwards break 
up and directly supply the material for the final accumu- 
lation of cheesy substance. The view which I derived 


* See a paper on tuberculosis and its relations to inflammation, secrofulosis and 
typhoid fever. Verhandlungen der physikalisch-medic. Gesellschaft zu Wiirzburg, 
1850, vol, i., p. 81. 


440 LECTURE XVIIL 


from these investigations of mine, namely, that a tissue 
undergoing hypertrophy may supply a completely ab- 
normal, diseased product, appeared to me all the more 
significant, because I had simultaneously detected an _ 
altogether similar series of developmental changes 
whilst examining an entirely different body, namely, the 
so-called typhous matter (Typhus-masse). At that time 
the view of the Vienna school had been universally 
adopted, that, in the different typhous processes, an exu- 
dation of an albuminous nature and soft, medullary charac- 
ter filled the parts, and that thereby swellings of a 
medullary appearance were produced. But whether 
the typhous matter be examined in the lymphatic glands 
of the mesentery, or round about the follicles of Peyer’s 
patches, no exudation capable of organization is at any 
time met with, but always a directly continuous deve- 
lopment from the pre-existing cellular elements of the 
glands, the follicles and the connective tissue, to the ty- 
phous matter. 

‘These observations were of course as yet insufficient 
to justify me in setting about effecting a general change 
in the existing doctrine, because we see organic elements 
arise at numberless points, where at that time at least 
cellular elements were altogether unknown to exist as 
normal constituents, and there was therefore scarcely 
any other explanation possible than that new germs 
were formed by a kind of generatio eequivoca [sponta- 
neous generation] out of the mass of blastema. The 
only places besides the glands, where such a develop- 
ment arising out of previously existing elements might 
have been inferred with some degree cf probability to 
take place, were the surfaces of the body with their 
epithelial elements. Then it was, that my investigations 
into the nature of the connective tissues, with which I 
have already so much plagued you, proved entirely de- 








PATHOLOGICAL AND EMBRYONIC NEW-FORMATION. 44] 


cisive. From the moment that I was able to maintain 
that there was scarcely any part of the body which did 
not possess cellular elements—that I could show that 
bone-corpuscles were real cells, and that connective 
tissue in different places contained, now a larger, now a 
smaller, number of really cellular elements—from that 
moment germs in abundance were supplied from which 
new tissues might possibly be developed. In fact, the 
more the number of observers increased, the more dis- 
tinctly was it shown, that by far the greater number of 
the new-formations which arise in the body proceed from 
connective tissue and its equivalents. From this rule 
comparatively few pathological new-formations are ex- 
cepted, and these belong on the one hand to the class of 
epithelial formations, and on the other are connected 
with the more highly organized tissues of a specific, ani- 
mal (p. 55) nature, for example, the vessels. We may 
therefore, with trifling restriction, substitute for the plastic 
lymph, the blastema of the earher, the exudation of the 
writers, connective tissue with its equivalents as the common 
stock of germs (Keimstock) of the body, and directty 
trace to it as the general source the development of 
new-formations. 

If we take a definite internal organ, for example, the 
brain or the liver, it was scarcely possible, as long as 
people saw nothing more than nervous matter in the 
brain, and admitted the existence of nothing more than 
vessels and hepatic cells in the liver, to imagine the oc- 
currence of a new-formation in them without the inter- 
vention of a special formative matter. For it was of 
course easy to convince oneself that new-formations do 
not in the liver usually proceed from the hepatic cells or 
the vessels. And that in the substance of the brain, the 
nerves as such do not give rise to new-formations, has 
been known ever since the microscope has been em- 


449 LECTURE XVIII. 


ployed, for since that time it has been known that 
medullary cancers are not due to the proliferation of 
nervous matter, but consist of cellular elements of 
another kind. In fact, the body appears to us at the 
present day, as Reichert was the first to note, to be 
made up of a more or less continuous mass of connec- 
tive tissue-like constituents, in which at certain points 
other things, such as muscles and nerves, are imbedded. 
Now it is in this more or less connected frame-work, 
that, according to my investigations, genuine new-forma- 
tion goes on, and that in accordance with the same law, 
which regulates embryonic development. 

This law of the correspondence between embryonic 
and pathological development was, as you know, laid 
down by Johannes Miiller, who continued the investiga- 
tions commenced by Schwann. But at that time the 
contents of an ovum were placed on a level with 
blastema ; it occurred to no one that the whole process 
of development in the ovum took place within the limits 
of a cell, but it was concluded simply, that there was 
a certain quantity of organizable material in the ovum, 
which—in virtue of a peculiar power innate in it, by 
means cf some organizing force, or as those would 
have it who regard the matter from a ‘ higher” point 
of view, impelled by an organizing idea—transformed 
itself into this or that particular shape. But here too 
the conviction has been gradually acquired, that the 
matter in question is a cellular substance, and if what 
has been most rigidly maintained by Remak is correct, 
namely, that the cleavage of the yolk also is due toa 
visible division of cells, to the growing in of mem- 
branous partitions into the interior of the ovum, and 
their coalescence, we have not here to deal with a free 
organizing impulse taking place within the yolk, but 
with progressive acts of division on the part of the 





ENDOGENOUS CELL-FORMATION. BROOD-CAVITIES. 443 


originally single cell. But long before this simple view 
of the process of the cleavage in the yolk had been 
arrived at, it had been very distinctly perceptible that in 
pathological processes a comparison between plastic exu- 
dations, or blastema, with the matters contained in the 
ovum, was obviously inadmissible, and that, where really 
formed parts were found, they had proceeded from a 
pre-existing part, a cell. 

The mode of origin of new formations is, as it seems, 
a double one. We have, namely, either to do with a 
simple division, such as we discussed when treating of 
irritation (p. 346). We then see the whole series of 


Fie. 124. 





Fig. 124. Proliferation of the growing cartilage of the diaphysis of the tibia of 
a child. Longitudinal section. a. The cartilage-cells on the border of the epiphy- 
sis, some of them simple, some of them in a state of commencing proliferation. 
6. Groups of cells that have arisen from the repeated division of simple cells, 
ce. Groups of cells lying near the calcifying border of the diaphysis, and considera- 
bly developed through the growth and enlargement of the individual cells; the 
intercellular substance growing continually more and more scanty. d. Section of a 
bloodvessel. 150 diameters. 


444 LECTURE XVIII. 


changes from the division of the nucleolus to the final 
division of the cell. If an epithelial cell acquires two 
nuclei, divides and this process is repeated, a long series 
of developmental changes may, by means of a continual 
repetition, be produced. If the skin becomes irritated — 
in consequence of continued friction, and the irritation 
is increased to a certain point, the epithelium will 
thicken, and if the proliferation is very energetic, it may 
lead to the production of tolerably large tumour-like 
formations. The same mode of development which is 
presented by layers of epithelium, we meet with also in 
the interior of organs. In cartilage, for example, where 
the individual cellular elements are inclosed in an inter- 
cellular substance, the place of each of them is at 
last occupied by an accumulation of numerous cells, 
the whole group, like the cell from which it proceeded, 
being shut off from its neighbors by the intercellular 
substance. This mode of development, therefore, is 
one which, though very simple in itself, may, since it 
originates in dissimilar parts, produce very different 
results. 

But we have besides another class of new-formations 


Fie, 125, 





Fig. 125. Endogenous new formation ; cells containing vesicles (physaliphores). 
A. From the thymus gland of a new-born infant together with epithelioid cells: in 
the interior of a vesicle which has a double contour (more distinctly marked in C’) 
and is besides surrounded by a cell-like border, lies a perfect nucleated cell. 
B. @. Cancer-cells (Cf. Archiv. fir pathol. Anatomie, Vol. IL, Pl. II., and Vol. III. 
Pl. II.) B, one with two nuclei; C, one with a physalid which nearly fills tne 
whole cell and another, where the physalid (brood-cavity) again encloses a perfect 
nucleated cell. 3800 diameters. 





BROOD-CAVITIES. 4AS 


in the body which are indeed much less well known, and 
of which the special peculiarities cannot as yet be seized 
with such great precision. These are processes, where 
we see endogenous changes set in in the interior of pre- 
existing cells. Ina simple cell a vesicular cavity forms, 
which, contrasted with the somewhat cloudy and gene- 
rally slightly granular contents of the cell, presents a 
very clear, bright, homogeneous appearance. In what 
manner cavities of this first kind, which I class together 
under the name of physaldes, arise, is not yet altogether 
certain. The greatest probabilities are in favour of the 
nuclei being, in certain forms, likewise the starting-poimt 


of these formations. For, beside these cells, others are 


seen with two nuclei, one of which, in several of them, 
has become somewhat larger and brighter than usual, 
though still preserving the character of a nucleus. Sub- 
sequently, this vesicle becomes so large that the cell is 
gradually almost entirely filled with it, and its former 
contents with the nucleus only look like a little appen- 
dage to the vesicle. So far the process is tolerably sim- 
ple. But besides these vesicles, thus growing and filling 
the cells, others are met with, in the interior of which 
elements of acellular nature are enclosed. This is of 
pretty frequent occurrence in cancerous tumours, but 


also in normal parts, for example in the thymus gland. 


This form seems to indicate, that in fact by means of a 
process which cannot be directly traced to any division 
of the pre-existing cells, and indeed in peculiar vesicular 
cavities (which I have named brood-cavities (or -vesicles 
—Brutraume), ) in the interior of cellular elements, new 
elements of a similar kind may be developed. How- 
ever, this is at all events a condition which plays but a 
subordinate part in the whole history of new-formations ; 
the regular form is the one first described. There are 
only a few pathological new-formations, in the history of 


446 LECTURE XVIII. 


which this endogenous development plays any distinct 
part, whilst in nearly all forms cell-division is met with 
to a great extent. 

The essential points of difference between the several 
modes of development of cells are therefore these: in © 
one class of formations the divisions proceed with a cer- 
tain regularity, so that the ultimate products from their 
very beginning exhibit a complete correspondence with 
the parent structures, and the young structures at no 
time deviate in any remarkable degree from the parent- 
cells. Such processes are in ordinary life mostly desig- 
nated as hypertrophies, but I have, in order to express 
the nature of the change more accurately, proposed 
the name of hyperplasie, inasmuch it is not an increase 
in the nutrition of existing parts that takes place, but a 
real formation of new elements (p. 94). 

In another class the development proceeds in such a 
way, that divisions certainly also do take place, but make 
very rapid progress and produce cells which gradually 
decrease in size, and ultimately in some instances be- 
come so small, that they can scarcely be distinguished to 
be cells. The proliferation may cease at this point, and 
then the cells severally begin to grow, and to become 
larger; and under certain circumstances a structure 
may in this case again also be produced analogous to 
that in which the development originated. This, how- 
ever, is not usually the case ; generally, the young cells 
pursue a somewhat different course of development, and 
a heterologous structure begins to form. 

The mode of development, which I here describe to 
you, may also run its course in such a way, that the 
cells do not at once begin to divide, but the nuclei first 
greatly multiply, becoming continually more numerous 
and at the same time smaller. We find something simi- 
lar to this in pus, in which a division of the nuclei very 





HOMOLOGOUS AND HETEROLOGOUS DEVELOPMENT. ‘AAT 


rapidly takes place, and generally in such a way, that 
the originally single nuclei at once divide into a consi- 
derable number of smaller ones, which at first remain 
coherent. But in pus it is not certain whether the divi- 
sion of the nucleus is succeeded by a real division in the 
cell, whilst in other new-formations this is certainly the 
case—only the complete division, or if you will, the 
cleavage, of the cells is delayed for a long time, and 
this intermediate stage of the mere division of the nu- 
clei continues for a disproportionately long period, and 
seems to occur in some sort independently. 

These two plans are the ones regularly followed by all 
those kinds of new-formations which do not directly lead 
to hyperplasia ;* the normal condition is here in the first 
instance interrupted by an intermediate state, in which 
the tissue appears essentially changed, without one’s 
being able straightway to determine whether a growth 
of a benignant or malignant nature will be developed 
out of it. This is a stage of seemingly absolute indif- 
ference; from the appearance of the individual ele- 
ments it cannot at all be inferred what their real destiny 
is ; they behave exactly like the so-called formative cells 
of the embryo, which also at first exactly resemble one 
another, no matter whether a muscular or nervous ele- 
ment, or anything else, is about to proceed from them. 
Nevertheless I regard it as very probable that delicate 
internal differences do really exist, which to a certain 
extent determine beforehand the subsequent metamor- 
phoses—not merely potential differences in the forma- 
tive cells, but really material differences, only of so 


* There are processes which begin with Hyperplasia and end with Heteroplasia, 
and others again, which begin with Heteroplasia and end with Hyperplasia. The 
new formation of vessels, for example, never begin straightway with the formation 
of vessels, but first of all cells are formed (heteroplasia), and afterward vessels (hy- 
perplasia) are developed out of these cells.—From a MS. Note by the Author. 


448 LECTURE XVIII. 


delicate a nature, that we are not as yet able to demon- 
strate them. 

In the development of the embryo a phenomenon has 
been known for years which positively indicates the ex- 
istence of such differences in the formative cells, inas- ° 
much as the different segments of the ovum run through 
their phases of development with different degrees of 
rapidity, and especially those parts which are destined 
to form the higher organs, run through their individual 
stages with much greater celerity than those whose lot it 
is to form the lower tissues. In the size of the cells 
also differences seem to exist. In a similar manner we 
frequently see that in pathological formations also differ- 
ences occur in reference to the time occupied in their de- 
velopment. Whenever the development of the cells 
takes place with great rapidity, we may be sure it isa 
more or less heterologous development. An homolo- 
gous, hyperplastic formation always presupposes a cer- 
tain tardiness in the processes which give rise to it; 
the cells generally remain of a larger size, since the di- 
visions do not usually proceed until very small forms are 
produced. 

Though so extremely simple in nature and in theory, 
these modes of development are certainly extremely dif- 
ficult of demonstration in individual places. The parts 
which apparently ought to be the most conveniently 
situated for the purpose of investigation, and in which 
Henle indeed, as long as twenty years ago, all but made 
the discovery of such a development, are the epithelia. 
Here, where a development often so abundant takes 
place upon the surface of a membrane, one would sup- 
pose it must be extremely easy to trace its course accu- 
rately in the individual cells. Henle, you know, en- 
deavoured to show that mucus-corpuscles, and indeed 
many forms which belong to pus, were produced on the 








EPITHELIOID NEW FORMATION. 449 


surface of mucous membranes along with the epithelium 
in such a way, that no real difference was to be per- 
ceived between the two classes in their earliest stages, 
and that the mucus-corpuscles must therefore in some 
sort be looked upon as epithelial cells that had gone 
astray, as children that had turned out ill, that had been 
impeded in the progress of their development by some 
early disturbance, but really were intended to become 
epithelial cells. Unfortunately the notion was then and 
long afterwards prevalent, that epithelium like all other 
tissues was normally developed out of a blastema. It 
was, you know, imagined that on the surface of every 
mucous membrane in the first instance there transuded a 
plastic fluid from the vessels running to the surface, and. 
that the epithelial cells were formed out of it. Schlei- 
den’s theory was steadfastly adhered to, that nuclei first 
form in a fluid, and that membranes do not develop 
around them until afterwards. At present, however 
much the different surfaces presented by the skin and 
the mucous and serous membranes are examined, the 
conviction is everywhere unmistakeably acquired, that 
the cellular elements extend down to the very surface of 
the connective tissue, and that there is nowhere a spot, 
where free nuclei, blastema or fluid exist, but that on 
the contrary it is especially the deepest layers which 
contain the most densely crowded cells. If, at the time 
when Henle made his investigations, it had been known, 
that no blastema ever exists in these parts, and that no 
development de novo ever takes place there, but that 
the epithelial cells there present must have been deve- 
loped either from old cells or from the connective tissue 
underneath them, he too would certainly also have 
come to the conclusion, that mucus- or pus-corpuscles 
which are not furnished by an ulcerating surface (which 


would of course be destitue of epithelium) must be 
29 


ABO LECTURE XVIII. 


derived by direct descent from pre-existing epithelial 
cells. 

So nearly, even at that time, had correct views upon. 
the subject been obtained, but the blastema theory 
enthralled men’s minds, and we all stood under its in- » 
fluence. Besides, it appeared impossible to point out 
everywhere in the interior of the tissues the requisite 
antecedent structures. Not until cellular elements had 
been shown to exist in connective tissue did it become 
possible to produce a germinal tissue (Keimgewebe) 
which is at present everywhere, and from which in the 
most various organs similar growths may be developed. 
Now that we know that connective tissue—or tissues 
equivalent to it—exists in the brain, the liver, the kid- 
neys, in muscle, cartilage, skin, etc., now there is of 
course no longer any difficulty in conceiving how the 
same pathological product may arise in all these appa- 
rently so dissimiliar structures. No specific blastema of 
any sort, deposited in all these parts, is at all required, 
but only the application of a similar stimulus to the con- 
nective tissue of the different localities. 

Now with regard to the details of this doctrine, allow 
me in the first place to bring to your notice a concrete 
example of normal development, which will perhaps be 
the best calculated to supply you with a picture of the 
often so complicated processes with which we are here 
concerned. I choose as my example that organ, in 
which the process of development is in itself best 
known, and which at the same time on account of the 
peculiarity of its structure least admits of misinterpreta- 
tion, namely the bones. They are too hard and thick 
for any one to talk about the presence of blastema or 
exudation in their proper parenchyma. The growth of 
the bones at the same time affords us direct standards 
wherewith to compare the different new-formations, 








é GROWTH OF BONE. 451 


which may occur in the bones in morbid conditions, for 
every one of these new-formations finds a certain proto- 
type in the normal development of bone. 

All the larger bones grow, as is well known, in two 
directions. This is most simply shown in the long bones, 
which gradually increase in length and thickness. The 
growth in length takes place from cartilage, that in 
thickness from periosteum. But a flat bone also is in- 
vested on the one hand with cartilaginous parts or their 
equivalents (sutures) and on the other with membranes 
which correspond to periosteum. A growth from carti- 
lage and a growth from periosteum can therefore be 
distinguished in every bone. This furnishes us with a 
plan of the development of long bones, which is found 
even in the writings of Havers, and according to which 
the new layers of bone incapsulate the old ones, and 
every more recent layer is not only wider but longer 
than that next above it in age. Hvery new layer of 
osseous substance which is formed out of periosteum is 
longer (higher) than the one immediately preceding it, 
inasmuch as new layers of perichondrium are being 
continually converted into periosteum. At the same 
time every new layer of osseous substance which grows 
out of cartilage is broader (thicker) than that which went 
before it, inasmuch as every new layer of the (growing) 
cartilage which proceeds to ossification surpasses its pre- 
decessor in breadth (thickness). The growth from car- 
tilage, however, can only take place in the direction of 
the extremities of the bone, inasmuch as the cartilage 
of its diaphysis is, at a very early period of intra-uterine 
life, so completely ossified,* that no cartilage remains ex- 

* This complete ossification in long bones is not confined to intra-uterine life, but 
every new layer of cartilage which grows out of the terminal cartilage up to the 
age of puberty ossifies (when matters follow a normal course) throughout its whole 


thickness, so that no cartilage remains at the circumference of the bone.—From a 
MS. Note by the Author. 


452 LECTURE XVIII. . 


cepting at the two ends. Now a tissue once ossified 
ceases (save under exceptional circumstances) to grow, 
so that any increase of thickness in the diaphysis must 
be wholly due to a development out of periosteum, in 
which growth proceeds much more slowly than in car- © 
tilage. This is the reason why the shaft of a long bone 
is narrower than its extremitics.* Whilst in this way 
parts which were previously either connective tissue or 
cartilage, are converted into bone, the development of 
the medullary tissue is going on within the bone. The 
original bone is extremely dense, a very solid and rela- 
tively compact mass. Subsequently the substance of 
the bone disappears more and more, one part of it after 
another is dissolved, and the medullary cavity [canal] 
arises, the size of which is not in any way restricted to 
that of the original osseous rudiment, but often conside- 
rably exceeds it. Thus the development of bone, when 
taken as a whole, does not consist merely in the gradual 
apposition of a succession of fresh osseous layers derived 
from periosteum and cartilage, but also in the continual re- 
placement of the innermost layers of the bone by masses 
of marrow. 

In the interpretation of these facts the blastema the- 
ory was long appealed to as the great authority. Havers 
and Duhamel, who made excellent investigations into 
the history of bone, started with the supposition that a 
nutritious juice (succus nutritius) was secreted, from 
which the new masses arose. The development of the 
marrow was imagined to consist in a formation of 
cavities, into which first a viscous juice and then a fatty 
matter was secreted—cavities which were invested by 
the medullary membrane, and whose contents varied 


* For a diagram of the growth of long bones, see Havers (Osteologia nova. 
Francof. 1692, Tab. I., fig. 1), and Kélliker (Handbuch d. Gewebelehre, 3d edit., 
Leipzig, 1859, p. 259). 








* 


FORMATION OF THE MARROW OF BONES. 453 


with age. However, as I have already poimted out to 
you, there are no sacs in the areole of the bones, but a 
continuous tissue, the medullary tissue, which fills the 
medullary spaces [cancelli] and cavities and belongs to 
the class of connective tissues, although it considerably 
differs from ordinary connective tissue. We have there- 
fore here to deal, as you see from this simple fact, with 
a substitution of tissues. As osseous tissue* is formed 
out of periosteum and cartilage, so marrow is formed 
from osseous tissue, and the development of a bone 
consists not merely in the formation of osseous tissue, 
but it presupposes that the series of transformations 
goes beyond the stage of bone, and that medullary 
tissue is, then produced. Medullary tissue therefore 
constitutes in some sort the physiological termination of 
the formation of bone as an organ. 

However simple this view may be, still it furnishes us 
with a picture of the growth and history of bone dif- 
ferent from the traditional one. Formerly, observers 
nearly always contented themselves with viewing the 
matter much in the same light that osteologists are wont 
to do; they took a macerated bone, examined it when 
divested of all its soft parts, and built up the processes 
accordingly. It is, however, necessary that the relations 
should be traced in the moist, living healthy or diseased 
bone, and that one should pay attention not only to the 
development of bone upon the outside from the growing 
layers of the cartilage and periosteum, but also to that 
of the medulla on the inside, as the ultimate product of 
the development in this class of tissues, even if it be 
not the noblest one. The most important and really 


* Osseous tissue (tela ossea, tissu osseux) = bone corpuscles + calcified inter- 
cellular substance. Bone as an organ = osseous tissue ++ medullary tissue + peri-¢ 
osteum -+- vessels + nerves. Osseous substance is sometimes taken to mean a por- 
tion of bone considered as an organ.— From a MS. Note by the Author. 


454 LECTURE XVIIL 


decisive point, through which the whole subject of bone 
acquires another aspect, is, I consider, this, that the 
bone in the formation of marrow is not simply dissolved 
and its place taken by some exudation or blastema, but 
that the dissolution of the osseous substance is a trans- 
formation of the osseous tissue, and that the dissolution 
results from a transformation of the intercellular sub- 
stance of the bone into a soft mass of tissue which is no 
longer in a condition to retain the calcareous salts. If 
therefore you ask whence the new elements come which 
arise in the midst of osseous tissue, or how a cancer or 
collection of pus can form in the middle of the compact 
cortex of bone, I return you the very simple answer, 
that they arise in precisely the same manner, that in the 
course of the natural and normal development of bone 
the marrow arises. In no part does the osseous tissue 
first dissolve, then an exudation, and next a new-forma- 
tion, follow, but the existing tissue is directly converted 
into the succeeding one. The existing osseous tissue is 
the matrix of the succeeding cancerous tissue, the cells 
of the cancer are the immediate descendants of the cells 
of the bone. 

If now we consider the course of the formation of 
bone a little more in detail, we find, as we have already 
in part seen, that the cartilage prepares for ossification 
in such a way, that its cells in the first instance become 
larger ; that divisions then take place in them, first in 
the nuclei and afterwards in the cells themselves ; that 
these divisions then proceed with great rapidity, so that 
we obtain larger and larger groups of cells, and in a 
comparatively short time the place of a single cell is 
occupied by a relatively very large group of cells (Fig. 
124). You will remember from my first lecture (p. 33), 
that a cartilage-cell is distinguished from most other 
cells by its secreting a special membranous capsule in 


GROWTH OF CARTILAGE. 455 


which it is inclosed. This membranous capsule, on the 
division of the cells which it contains, sends in septa 
between them, which serve as new envelopes for the 
young cells, yet in such a way, that even the gigantic 
groups of cells, which proceed from each of the original 
cells, are still enclosed in the greatly enlarged parent 
capsule. 

It is manifest, that the greater the number of: cells 
which undergo this change, the larger the cartilage will 
become, and that the height to which any one of us 


Fie. 126. 


W 


I? x = = 


x 


S 
\ 


Ta, ga Xs 
WS 





TILED 


VB 
> WN 
WANS 
as : 


S| 
IWS WX KS 
. POY 
\N 


N 


Fig. 126. Vertical section through the ossifying border of a growing astragalus. 
ce. Cartilage with smallish groups of cells, p, the layer where the proliferation and 
enlargement are the most marked along the line of calcification. In the cartilage- 
cavities are seen, partly complete nucleated cells, partly shrivelled, angular and 
granular looking bodies (artificially altered cells). The dark mass advancing into 
the intermmediate substance represents the deposition of calcareous salts, behind 
which the formation of medullary spaces (m, m, m) and osseous trabecule [spicula] 
is here beginning with unusual rapidity. The marrow has been removed; round 
the cavities which lie farthest back, the trabecule are surrounded by a lighter bor- 
der of young osseous tissue (produced from marrow.) 300 diameters. 


456 LECTURE XVIII. 


attains, essentially depends upon the extent to which 
growth occurs in the individual groups of cartilage-cells. 
Whether we ultimately become tall or short, is, if I may 
say so, left entirely to the discretion of these elements. 
When the growth of the proliferating cartilage has © 
reached this point, the cellular elements are very close 
together, so that a comparatively trifling quantity of 
intereellular substance lies between them (Fig. 124). 
The farther the development advances, the more does 
the appearance of the cartilage alter, and at last it looks 
almost like dense-celled vegetable tissue. The cells 
themselves however are difficult to be seen, because they 
are extremely sensitive ; they readily shrivel up upon 
the addition of the mildest fluids and then appear like 
angular and jagged corpuscles, almost analogous to those 
of bone, with which however they have at this time 
_ nothing to do. 

The cells which have sprung from this excessive proli- 
feration of the originally simple cartilage cells, consti- 
tute the parent structures from which proceeds all that 
afterwards arises in the longitudinal axis of the bone, 
and especially the osseous and medullary tissue. The 
cartilage-cells may be converted by a direct transforma- 
tion into marrow-cells and continue as such; or they 
may first be converted into osseous, and then into me- 
dullary, tissue; or lastly they may first be ,converted 
into marrow and then into bone. So variable are the 
permutations of these tissues in themselves so nearly 
allied, and yet in their external appearance so com- 
pletely distinct. When a direct transformation into 
marrow is the first effected, the eld intercellular sub- 
stance of the cartilage at the. border next to the bone 
begins first of all to grow soft; then some of the ad- 
joining capsules usually also very soon experience this 
change, so that the cellular elements come to be more 








TRANSFORMATION OF CARTILAGE. 457 


or less set free in a softer basis-substance. Simultane- 
ously with the occurrence of this softening the chemical 
reaction of this tissue also becomes altered, and we 
always obtain the distinct reaction of mucin. At the 
same time divisions begin to take place, and this not in 
the same way as previously, when the cellular elements 
at once separated into two new analogous cells (hyper- 
plasia), but rather in such a way, that a number of little 
nuclei arise in them (physiological heteroplasia). Sub- 
sequently, in proportion as this process of transforma- 
tion reaches a higher and higher pitch, and fresh por- 
tions of the intercellular substance are continually ‘being 
converted into this more homogeneous and soft matter, 
the cells generally divide, and we obtain a number of 
smaller ones, which are very minute in comparison to 
the large cartilage-cells, from which they proceeded, and 
contain either a single nucleus with a nucleolus, or 
sometimes also, like pus-corpuscles, several nuclei. 
Thus gradually arises a tissue extremely rich in cells, 
the young, red, medullary tissue, as we generally find it 
in the marrow of new-born infants. If the process 
stops here, the size of the transformed spot indicates 
at the same time the extent of the subsequent medul- 
lary space. Subsequently, these little cells may take up 
fat, and then it appears, first in small granules, but by 
degrees in large drops, and at last to such an extent that 
the cells are entirely filled with them. Thereby the 
original medullary tissue is transformed into adipose 
tissue ; the fat, however, is always contained in the 
interior of the marrow-cells, as it is in the cells of the 
panniculus adiposis. But this yellow, fatty marrow does 
not occur in all bones. In the bodies of the vertebree 
we almost always find the small cells. In the long 
bones of the adult the fatty marrow always occurs 
normally, but in pathological conditions it may very 


458 LECTURE XVIII. 


rapidly yield up its fat, the elements may divide and we 
then again have red, but inflammatory, marrow. 

In this whole series of allied processes from the first 
development of marrow out of cartilage until the pro- 
duction of inflammatory marrow—the last disturbance 
which manifests itself in injured bones (as we see in 
amputations)—there at no time exists any amorphous 
substance, blastema or exudation ; we can always trace 
the descent of one cell from another ; every one of them 
has been directly developed from an earlier one, and 
will have as long as the proliferation continues, a direct 
progeny of cells. 

The second series of transformations in the longitudi- 
nal axis of the cylindrical [long] bones is furnished by 
the osseous tissue, which may arise out of marrow and 
cartilage. In the one case the marrow-, in the other, 
the cartilage-cells, become the subsequent bone cells. 
This act of real ossification, the production of the osse- 
ous tissue, is extremely difficult to observe, chiefly for 
the reason, that what first takes place in the course of 
these processes, is not the production of real osseous 
tissue, but only the deposition of calcareous salts. Gene- 
rally, namely, there first of all takes place in the imme- 
diate vicinity of the border of the bone a calcification 
of the cartilage, which gradually advances, first along 
the borders of the larger groups of cells, and then 
around the individual cells, always following the sub- 
stance of the capsules, so that every individual cartilage- 
cell is surrounded by a ring of calcareous substance. 
But this is not yet bone, it is nothing more than calcified 
cartilage, for, upon dissolving the calcareous salts, the 
old cartilage is again brought into view—and indeed it 
offers no analogy to bone in any other respect excepting 
in the presence of calcareous salts. 

Now, in order that this calcified cartilage may become 


CALCIFICATION OF CARTILAGE. 459 


Fre. 127. 








Fig. 127. Horizontal section through the growing cartilage of the diaphysis of 
the tibia of a seven months’ foetus. Cc. The cartilage with groups of cells that 
have undergone proliferation and enlargement; p p, perichondrium. &. Calcified 
cartilage, in which the individual groups of cells, and cells, are enclosed in calcare- 


ous rings; at #’ larger rings, at k” progress of the calcification along the perichon- 
drium. 150 diameters. 


Fig. 128. Right corner of Fig. 127, more highly magnified. co. Calcified cartilage 
co’ commencement of calcification, p perichondrium. 350 diameters. 


460 LECTURE XVIII. 


real bone, it is necessary that the cavity in which every 
cartilage-cell lies, be converted into the well-known, 
radiated, jagged bone-cavity [lacuna]. This process is 
so extremely difficult to obtain a sight of, because on 
making sections the masses of lime crumble away before 
the knife, and furnish débris within which it is impossi- 
ble to see well what really is present. In this circum- 
stance you must seek for an explanation of the fact, that 
up to the present time there are still, and probably still 
will be for several years, continual disputes with regard 
to the mode of origin of bone corpuscles. I hold that 
view to be correct, according to which the bone-cor- 
puscles* in certain places directly originate out of the 
the cartilage-corpuscles, and indeed in this way, that in 
the first place the cavity of the capsule which invests 
the cartilage-cell, becomes narrower, manifestly because 
fresh capsular matter is deposited on the inside. But 
in proportion as this takes place, the inner border of the 
capsular cavity begins to assume a distinctly indented ap- 
pearancey (Fig. 133, c’) and the space occupied by the 
original cell is thereby considerably diminished. In rare 


* Cartilage-corpuscle = capsule + cartilage-cell; bone-corpuscle = bone-cell.— 
Transl. 

+ The lacune may be said really to have no existence in diving bone (or osteoid 
tissue) ; they are merely the gaps (holes) in the intercellular substance in which 
the bone- (or osteoid-) cells lie, and are normally so entirely filled by these cells, 
that it is impossible to give the outlines of both in a drawing. The outline of the 
cell is the outline of the lacuna. Who, in drawing a deal-board, would ever think 
of giving a second contour to every knot, in order to represent the outline of the 
gap which would result from the falling out of the knot! Hence Authors have 
come to speak of the nuclei of lacune, whereby of course they mean the nuclei of 
the cells which fill the lacunz, but which, thanks to the deeply rooted but errone- 
ous impression left upon their minds by microscopical sections of macerated bone, 
they have failed to recognize, or have not even sought for, taking for granted they 
had lacune before them. In the preparation of sections, however, the cells frequently 
shrink, so that an interval is left between them and the walls of the lacune. 

What is here said of the lacunew of course equally applies to the canaliculi. 
Both represent the margins of the calcified intercellular substance, where it comes 


into contact with the bone-cells and their processes. —Based upon MS. Notes by the 
Author. 





FORMATION OF BONE-CORPUSCLES. 461 


cases, we still succeed in finding cartilage-corpuscles, in 
which the capsular cavity-has (without the occurrence 
of calcification) become diminished in consequence of 
the deposition of new capsular matter, so as to assume 
the form of a bone cavity (lacuna)—which it generally 
assumes only after ossification—whilst the old cellular 
element (the cartilage-cell with its nucleus) still remains 
in it. After this—still without the occurrence of any 
calcification—the boundary disappears which originally 
existed between the capsules of the cartilage-cells and 
the basis-substance, and we find jagged elements* (the 
future bone-cells) in an apparently entirely homogeneous 
substance—in other words, a tissue still soft, though in 
structure like bone (osteoid tissue, Fig. 133, 0). Usually 
this process is concealed by means of the early calcifi- 
cation of the cartilage and only certain processes, for 
example, rickets, give us the opportunity of seeing the 
osteoid transformation take place in just the same man- 
ner in those parts of the cartilage also which are begin- 
ning to calcify. 

But the old limits of the capsule still represent the real 
district which is under the sway of the bone-corpuscule, 
and, as I pointed out to you at the commencement of my 
lectures (p. 41) with an especial reference to this point, 
in pathological conditions this district comes again not only 
in force but also into view. Within these limits we see 
the bone-corpuscle accomplish its peculiar destinies. If, 
for example, the bone is by any cause impelled to enter 


* The cartilage-cells (and the same holds good of the marrow-cells) during ossi- 
fication throw out processes (become jagged) in the same way that connective-tis- 
sue corpuscles, which are also originally round, do, both physiologically and patho- 
logically. These processes—which in the case of the cartilage-cells are generally 
formed after, but in that of the marrow-cells frequently before, calcification has taken 
place—bore their way into the intercellular substance, like the villi of the chorion 
do into the mucous membrane and into the vessels of the uterus, or like the pac- 
chionian granulations (glands) of the pia mater of the brain into (and occasionally 
through) the calvarium.—From a MS. Note by the Author. 


462 LECTURE XVIII. 


upon new transformations, one bone-corpuscle after 
another with its territory experiences the change. At 
the border of necrosed portions of bone, when the line of 
demarcation forms, we may distinctly observe, that the 
surface of the bone, when viewed along the edge, becomes 
marked with excavations, the extent of which corresponds 
to the original cells. Upon the surface vacuities are 
observable, which in some instances run together and 
form holes. The bone-corpuscle which formerly occu- 
pied the site of the hole has, in proportion as it under- 


‘ Fig 129.* 





OOOO 
SAAS S 











\\ = WAX 
~~ <N Rh 
WYK \ WS 





YG, 
Z 
OGG ff 
Ui 7G. Ui 
A, > Yt, 
, Z 
% 
L, 





Gy 


Fig. 129. Line of demarcation in a piece of necrosed bone from a case of pedar- 
throcase ; + a, a, a the necrosed bone with very much enlarged osseous corpuscles 
and canaliculi; here and there slight indications of excavations upon the surface. 
6, 6. The vacuities, which have taken the place of the cell-districts of the bone (Cf. 
Fig. 184), seen at the side of the object on a different level ; here and there enlarged 
bone-corpuscles still to be seen through a layer of basis-substance which covers 
them. c, c. Completely empty cavities. 300 diameters. 


* The drawing was made from a somewhat thick preparation, and does not repre- 
sent one level surface, but three different planes which form, as it were, terraces, 
one above the other. Of these ¢ is distinctly in focus; 6 is on a lower (or higher) 
level, and is less distinctly seen; a is lower (or higher) still, and is therefore still 
more out of focus. Hence it is that the canaliculi (which besides are badly repre- 
sented), are not clearly seen.—From a MS. Note by the Author. 

+ Necrosis (scrofulous) of the fingers in children. 


CARIES. 463 


went transformation itself, also determined the surround- 
ing parts to enter upon the change. These are the 
processes, without the aid of which it is impossible to 
comprehend the history of caries.. For the whole essence 
of caries consists in this : the bone breaks up into its ter- 
ritories, the individual corpuscles undergo new develop- 
mental changes (granulation, suppuration), and remnants * 
composed of the oldest basis-substance remain in the form 
of small, thin shreds in the midst of the soft substance. 
I traced this out again only to-day in a stump, in which, 
a fortnight after amputation, periostitis with slight sup- 
puration and incipient peripheral caries was found to 
exist. When in such a case the thickened periosteum is 
stripped off, we see, at the moment it quits the surface 
and the vessels are drawn out from the cortex of the bone, 
not, as in normal bone, mere threads, but little plugs, 
thicker masses of substance; and if they have been 
entirely drawn out, there remains a disproportionately 
large hole, much more extensive than it would be under 
normal circumstances. On examining one of these plugs 
you will find that around the vessel a certain quantity of 
soft tissue lies, the cellular elements of which are in a 
state of fatty degeneration. At the spot where the vessel 
has been drawn out, the surface does not appear even, as 
in normal bone, but rough and porous, and when placed 


* In ossification (in cartilage) there is a portion of the original intercellular sub- 
stance of the cartilage—that, namely, which lies between the large groups of carti- 
lage-cells (secondary cells—Tochterzellen)—which, though it belongs to the groups 
as wholes, yet when these, in the course of ossification, are transformed into a num- 
ber of isolated bone-cells, becomes, comparatively speaking, almost entirely inde- 
pendent of these cells individually (which have their own immediate intercellular 
substance to attend to, and from most of which it must be separated by a considera- 
ble interval), and therefore escapes the changes which befall them. It is this 
portion (well shown in Fig. 126, where it is represented by the trabecule separating 
the medullary spaces m), which remains behind in caries, whilst the secondary inter- 
cellular substance perishes. In other processes, however, which run a more chronic 
course (in cancer, for example), everything is destroyed. Based upon MS. notes by 
the Author. 


464 LECTURE XVIII. 


under the microscope, you remark those excavations, 
those peculiar holes, which correspond to the liquefying 
bone-territories. If it be asked therefore in what way 
bone becomes porous in the early stage of caries, it may 
be said that the porosity is certainly not due to the for- — 
mation of exudations, seeing that for these there is no 
room, inasmuch as the vessels within the medullary canals 
(Figs. 32, 33) are in immediate contact with the osseous 
tissue. On the contrary, the substance of the bone in 
the cellular territories liquefies, vacuities form, which are 
at first filled with a soft substance, composed of a slightly 
streaky connective tissue with fattily degenerated cells. 
If round about a medullary canal the territory of one 
bone-corpuscle after another liquefies, you will after a 
time find the canal bounded on all sides by a lacunar 
structure. In the middle of it the vessel conveying the 
blood still remains, but the substance around about is not 
bone or exudation, but degenerate tissue. The whole 
process is a degenerative ostitis, in which the osseous tissue 
changes its structure, loses its chemical and morphological 
characters, and so becomes a soft tissue which no longer 
contains lime. The tissue, which fills the resulting 
vacuity in the bone, may vary extremely according to 
circumstances, consisting in one case of a fattily degene- 
rating and disintegrating substance (the bone-corpuscles 
perishing), and in another of a substance rich in cells and 
containing numerous young cells ; this latter is formed by 
the division and proliferation of the bone-corpuscles, and 
the newly produced substance is very analogous to mar- 
row. Under certain circumstances this substance may 
grow to such an extent, that—if we again borrow our 
illustration from the surface of the bone, where a vessel 
sinks in—the young medullary matter sprouts out by the 
side of the vessel, and appears as a little knob, filling one 
of the pits in the surface. This we call a granulation. 


GRANULATIONS, PUS. 465 


When we examine granulations for the purpose of 
comparing them with medullary tissue, we find that no 
two descriptions of tissue more closely correspond. ‘The 
marrow of the bones of a new-born infant could at any 
time, both chemically and microscopically, be passed off 
as a granulation. Granulations are nothing more thana 
young, soft, mucous tissue, analogous to marrow. There 
is an inflammatory osteoporosis, which, as has been cor- 
rectly stated, merely depends upon an increased produc- 
tion of medullary spaces, so that the process which is 
quite normal in the interior of a medullary cavity, is met 
with also more externally in the compact cortex. It (the 
osteoporosis) is distinguished from granulating peripheral 
caries only by its seat. If you go a step further and 
suppose the cells, which in osteoporosis are present in 
moderately large numbers, to become more and more 
abundant, whilst the intercellular substance constantly 
becomes softer and diminishes in quantity, we have pus. 
The pus is here no special product, separable from the 
other products of proliferation and formation ; it is cer- 
tainly not identical with the pre-existing tissues, but its 
origin can be directly traced back to the elements of the 
pre-existing tissue. It is not produced by any special 
act, by any creation de novo, but its development pro- 
ceeds from generation to generation in a perfectly regular’ 
and legitimate manner. 

We have therefore before us a whole series of trans- 
formations ; the bone first produced and proceeding from 
cartilage may undergo a transformation into marrow, 
then into granulation-tissue, and finally into nearly pure 
pus. The transitions are here so gradual, that the pus 
which is in immediate contact with the granulations, con- 
stitutes, as is well known, a more mucous, stringy, and 
tenacious matter, which really contains mucin like the 


granulation-tissue, and only when we proceed farther out- 
30 


466 LECTURE XVIII. 


wards, exhibits the properties of completely developed 
pus. The perfect pus of the surface gradually passes, as 
we descend, into crude pus, the mucous, tenacious, imma- 
ture pus of the deeper layers, and what we call matura- 
tion depends simply upon the gradual conversion of the © 
mucous intercellular substance of the originally tenacious 
pus, which is allied in structure to granulations, into the 
albuminous intercellular substance of pure pus. The 
mucus dissolves and the creamy fluid is produced. The 
maturation ts therefore essentially a softening of the inter- 
cellular substance. So direct is the connection which sub- 
sists between development, and retrograde metamor- 
phosis, physiological and pathological conditions. 

In just the same manner that the cartilage-cell may 
become a bone corpuscle, the marrow-cell also may become 
a bone-corpuscle. In the medullary spaces of bone those 
marrow-cells which are situated at the circumference, 
generally assume at a later period a more oblong form, 
and take a direction parallel to the internal surface of 
the medullary spaces, and the medullary tissue in this 
situation has a more fibrous appearance and has indeed 
been regarded as a medullary membrane, but it should 
not be separated from the marrow in the centre of the 
‘spaces, and only constitutes the most compact layer of 
the medullary tissue. Now as soon as osseous tissue is 
about to form, the nature of the basis-substance alters. 
It becomes firmer, more cartilaginous, and the individual 
cells appear to lie in largish cavities. Gradually they 
become jagged, from sending out little processes, and 
then nothing more is required than that calcareous salts 
should deposit themselves in the basis-substance—and 
the bone is complete. Thus here again also the osseous 
tissue 1s formed by a very direct transformation ; and by 
the deposition of one such osteoid * layer after another 


* Osteoid I call the tissue which, when it takes up calcareous salts, becomes bone, 


DEVELOPMENT OF BONE OUT OF PERIOSTEUM. 467 


from the medulla, a compact substance is produced, like 
that of the cortex, which is always characterized by the 
lamellar deposition of osseous tissue in the previously ex- 
isting medullary spaces. The original bone is always 
. pumice-stone-like, and porous ; its porosities become filled 
by the subsequent development of osseous lamelle from 
the layers of the marrow, the process continuing until 
the vessel, which does not admit of ossification, alone re- 
mains. 

Now with regard to the development of bones in thick- 
ness, the process is in itself much simpler, bué it is also 
at the same time very much more difficult to see, be- 
cause ossification here proceeds very rapidly, and the 
proliferating periosteal layer is so thin and delicate, that 
extremely great care is required in order to catch sight 
of it at all. Pathology furnishes us with an incompara-_ 
bly better opportunity for studying the process than 
physiology. For it is just the same whether the bone 
grows physiologically in thickness, or pathologically in 
consequence of periostitis ; the difference is only one of 
quantity and time. 

When fully developed, the periosteum consists for the 
most part of a very dense connective tissue which con- 
tains an extremely large quantity of elastic fibres, and 
in which the vessels ramify, before they pass on into 
the cortex of the bone itself. Now when the growth 
of the bone in thickness commences, we see that the 
most internal, vascular layer (of the periosteum) in- 
creases in thickness and swells up, and then it is said an 
exudation has taken place, it being taken for granted, 
that every swelling proves the occurrence of an exuda- 
tion, and that the exudation here lies between the peri- 
osteum and the bone. But if you set to work and 


—in other words, soft, uncalcified, osseous tissue.—From a MS. Note by the 
Author. 


468 LECTURE XVIII. 


analyze the substance deposited, no trace of any plastic 
exudation is found; thé ‘swollen spot appears on the 
contrary organized in its whole thickness from without 
inwards, and this most distinctly close to the bone, 
whilst towards the surface of the periosteum the struc- 
tural relations can be less readily unravelled. This 
swelling may under certain circumstance increases to a 
very considerable extent. In 
periostitis we do not unfre- 
quently see, you know, regu- 
lar nodes formed, and one 
need only recall the more 
physiological history of callus 
after fracture. In either of 
these cases we seek in vain 
for an exudation. If the 
thickened layers are traced in 
the direction of that part of 
the periosteum which still re- 
mains unthickened, we can 
very distinctly see what Du- 
hamel long ago exhibited in a very beautiful manner, 
but is forgotten over and over again, namely, that the 
layers which constitute the thickening are ultimately all 
of them continued into the layers of the periosteum. 
As little as the periosteum is unorganized, so little are 
the thickened layers without organization. Microscopi- 
cal examination shows at the surface of the bone a 
slightly striated basis-substance, and in it, numerous, 


Hre. 130: 





Fig. 130. Vertical section through the periosteum and periosteal surface of a 
parietal bone from a child. A. The proliferating layer of the periosteum with - 
anastomosing networks of cells and division of nuclei. 2B. Formation of the 


osteoid layer by means of the sclerosis* of the intercellular substance. 3800 
diameters. 


* Sclerosis signifies thickening with condensation.—From a MS. Note by the 
Author. 


OSTEOID TISSUE. 469 


small, cellular elements ; the farther we recede from the 
bone, the more do divisions of cells oceur, and at last 
we meet with the simple, very small connective-tissue- 
corpuscles of the periosteum. The division follows the 
same course as in cartilage, only that the dividing cells 
of the periosteum are very delicate. The greater the 
irritation, the greater also the proliferation, and the 
more considerable the swelling of the growing spot. 

The cells which thus result from the proliferation of 
the periosteal corpuscles are converted into bone-cor- 
puscles exactly in the way I described when speaking 
of the marrow. In the neighbourhood of the surface of 
the bone the intercellular substance grows dense and 
becomes almost cartilaginous, the cells throw out pro- 
cesses, become stellate, and at last the calcification of 
the intercellular substance ensues. If the irritation is 
very great, the corpuscles grow very considerably, and 
then real cartilage is produced ; the corpuscles enlarge 
to such an extent that they grow into large, oval or 
round cells, and each of these forms a capsule around 
itself by secretion. In this manner cartilage may arise 
in the periosteum also, by means of a direct transforma- 
tion of its proliferating layers, but it is by no means 
necessary that real, true cartilage should be produced ; 
generally only the osteoid transformation takes place, 
when the intercellular substance becomes sclerotic and at 
once calcifies. 

Thus it is, that on the surface of every growing bone, 
as Flourens particularly has shown, new bone is continu- 
ally deposited layer after layer, and that the new layers 
grow round the old bone in such a way, that a ring, 
which is early put around the bone, after a time lies 
inside it, enclosed by the young layers which have 
formed outside around it. These are connected with 
the old bone by means of little columns which give the 


470 LECTURE XVIII. 


whole a pumice-stone like appearance, and here too the 
subsequent condensation into cortical substance is ac- 
complished by means of the formation—within the 
individual cavities bounded by the little columns—of 
concentric layers of osseous substance out of the perios- — 
teal marrow. 

These are the normal and pathological processes which 
we recognize in the formation of bone. From them you 
may gather, that we have in them to do with a series of 
permutations or substitutions, which lead in one case to 
a higher, in another, to a lower form of structure, but 
are however constantly connected with one another, 
and, according to the conditions which operate upon the 
parts, assume sometimes one aspect, sometimes another. 
It is in our power to incite individual portions of carti- 
lage to ossify, or to transform themselves into a soft 
tissue. In this whole series the marrow stands alone as 
the type of the heterologous forms, inasmuch as it con- 
tains the smallest and least characteristic cells. The 
young medullary tissue presents the same structure as 
the young formations, with which all heterologous 
tissues begin, and since, as I have already hinted, it at 
the same time constitutes the real type of all granula- 
tions, it may be said that, wherever new-formations are 
about to arise on a large scale, a substitution analogous to 
the type of young medullary tissue (granulation) also takes 
place; and that, no matter how great the solidity pos- 
sessed by the old tissue, a kind of proliferation neverthe- 
less always takes place, which produces the germs of the 
subsequent elements. 


dd kia ddd eed 


APRIL 24, 1858. 


PATHOLOGIOAL, AND ESPECIALLY HETEROLOGOUS NEW- 
FORMATION. 


Consideration of some forms of pathological formation of bone. Soft osteoma of 
the maxille—Rickets—Formation of callus after fracture. 

Theory of substitutive new-formation in opposition to exudative—Destructive 
nature of new-formations—Homology and heterology (malignity)—Ulcera- 
tion—Mollities ossium—Proliferation and luxuriation—Medulla of bones, and 
pus. . 

Suppuration—Its two forms: superficial, occurring in epithelium; and deep, in con- 
nective tissue—Eroding suppuration (skin, mucous membrane) : pus and mucus- 
corpuscles in their relations to epithelium—Ulcerative suppuration—Solvent 
properties of pus. 

Connection of destruction with pathological growth and proliferation—Correspon- 
dence of the first stage in pus, cancer, sarcoma, etc.—Possible duration of the 
life of pathologically new-formed elements, and of pathological new-formations 
considered as wholes (tumours)—Compound nature of the larger tuberous* tu- 
mours (Geschwulstknoten), and miliary character of the real foci (Heerde)— 
Conditions of growth and recurrence: contagiousness of new-formations and 
importance of the anastomoses of cells—Cellular pathology in opposition to 
the humoral and neuristic—General infection of the body—Parasitism and 
autonomy of new-formations. 


GENTLEMEN,—I will to-day begin by laying some 
pathological preparations before you, for which I re- 
mained in your debt last time. 

I begin with an interesting object which has lately 
come into my hands, and exhibits with a distinctness 


* Tuberous, in contradistinction to infiltrated, tumours (infiltrations).—From a 
MS. Note by the Author. 
471 


“472 LECTURE XIX. 


which I have rarely had occasion to witness, the transi- 
tions from periosteal connective tissue into osteoid tis- 
sue, and this too with a peculiar modification, inasmuch 
as calcification has not taken place in large portions of 
the parts which already possess a structure of bone. The 
preparation comes from a tumour in the jaw of a goat, 
and contributes towards our knowledge of the transi- 
tions from connective tissue into osteoid tissue about 
the same information, that the history of rickets has 
supplied us with concerning the transformation of carti- 
lage. The tumour which affected the superior and infe- 
rior maxille, but each separately, has such little density, 
that it can be cut with great facility, and only in a few 
places does the knife meet with greater resistance. On 
making thin sections, we see, even with the naked eye, 
that the more and less dense portions alternate with 
each other, so that the whole has a reticular appearance. 
When examined under the microscope with a low power, 








Fig. 151. Section from the soft osteoma from the jaw of a goat—showing the 
characters of periosteal ossification. Networks of osteoid trabecule with jagged 
cells enclose primary medullary spaces, filled with fibrous connective tissue, The 
dark parts represent calcified and completely developed osseous tissue. 150 dia- 
meters, 


4 
» epee 
SB ky 





PERIOSTEAL OSSIFICATION. 473 


it is'at once perceived that the disposition of the con- 
stituent parts is entirely that of a bone, for (primary*) 
medullary spaces and trabecular networks alternate with 
each other, just as if the observer had before him the 
medullary spaces and trabecule of a spongy bone. 
The substance which forms the trabecular networks, 
is on the whole dense, and is therefore readily distin- 
guishable, even with a low power, from the more: deli- 
cate substance which is enclosed by the trabecule and 
fills the cavities of the meshes. This latter substance 
presents, when more highly magnified, a finely striated 
fibrous appearance. The bands of fibres in part run 
parallel to the borders of the trabecule. In these latter 
the same structures can be seen with a high power, that 
are usually presented by the bone, namely jagged cor- 
puscles, distributed with great regularity. 

This structure exactly corresponds to that which we 
have seen in the development of bone from periosteum ; 
it is, in short, the plan followed in the growth of bone in 
thickness. Wherever young periosteal deposits are ex- 
amined, there is found in the meshes of the network, 
formed by the osteoid substance, this primary marrow 
containing fibres, but no cells, as is the case at a later 
period. This primary marrow consists of the remains of 
the periosteum itself (after its proliferation), which have 
not yet undergone the transformation. The transforma- 
tion into osteoid tissue advances into the proliferating 
periosteum in the first instance always in such a way, 


* The primary medullary spaces formed out of periosteum are subsequently 
all filled with compact bone, and it is by the conversion of this into true mucous 
medullary tissue, abounding in cells (which afterwards take up fat) that the 
secondary medullary spaces are formed. Of the primary medullary spaces formed 
out of cartilage, however, a considerable number do not pass through any 
such intermediate stage as that just described as occurring in periosteal ossifi- 
cation, but become ot once filled with true medullary tissue and are therefore 
equivalent to the ordinary, secondary medullary spaces.—From a MS. Note by the 
Author. 


474 LECTURE: XIX. 


that the fibrous tissue becomes condensed (sclerotic), 
though only partially so, the condensation beginning at 
the bone and proceeding outwards in certain directions ; 
in this way there arise, at first resting like columns upon 
the bone, hardish cones * which are united by transverse’ 
bands, parallel to the surface of the bone, and thus con- 


Nie. 132: 









Yi fgg 











SW 






SS 
SSS 
SSS 
SSS S 
SS 


SAK 
3 WSN SS 







S SS 
SS SSS 






SSS 
SS 








stitute this network. If now acetic acid be applied to 
these parts, we see at once that the whole fibrous mass 
which fills the alveoli, contains the most wonderful con- 
nective-tissue-corpuscles, which are so arranged, that 
next to the trabeculee all around they lie in concentric 
rows, whilst in the most internal parts of the marrow 
they constitute stellate corpuscles which anastomose with 
one another, as you have already seen on many occasions. 
But that in some parts the trabecule have already 
become true bone, one may very beautifully convince 


Fig. 132. A portion of Fig. 181, more highly magnified. 0, 0. The osteoid tra- 
becule ; m, m, m the primary medullary spaces with spindle-shaped and reticulating 
cells. 300 diameters. 


* These are the little columns mentioned in p. 110 as being perpendicular to the 
long axis of the bone, and as intervening between the Haversian system—Transi. 


FORMATION OF BONE FROM CONNECTIVE TISSUE. 475 


oneself at the spots, where calcareous salts are really 
deposited in them. Whilst the periphery of such calcified 
trabecule (Fig. 131) offers a brilliant, almost cartilagi- 
nous appearance, in their middle an opaque, finely gra- 
nular matter presents itself which pervades the intercel- 
lular substance, and towards the interior of the trabecule 
passes into a nearly homogeneous, calcareous layer, in 
which at intervals the osseous corpuscles may be recog- 
nized. Here we have therefore already a complete 
osseous network, and at the same time an exact picture 
of the regular growth of bone in thickness. 

If, however, the spots are very carefully examined, 
where the borders of these trabeculz and bands of bone 
come into contact with the fibrous substance of the 
meshes, it is seen that no perfectly defined limit exists 
there, but that the mtercellular substance of the osteoid 
tissue is gradually lost in the intercellular substance of the 
fibrous marrow, so that here and there a few of the con- 
nective-tissue-corpuscles of the fibrous connective tissue 
are included in the sclerotic substance of the trabecule. 
Hence you may infer, that the formation of the real osse- 
ous substance from connective tissue is essentially effected 
by the gradual change of the intercellular substance, and 
that this loses its originally fibrous nature and becomes 
converted into a dense, shining, cartilaginous mass, with- 
out its ever really attaining however to the structure of 
cartilage. Here there is never a stage exactly corres- 
ponding to any of the known forms of cartilage, but it is 
out of connective tissue that we see the osteoid substance 
directly arise, which in cartilage also and marrow is the 
first to arise when they become bone. Thisis so far very 
important, that you can from all these instances acquire 
the conviction that people have been mistaken in speak- 
ing of the cartilage of bone (Knochenknorpel). Cartilage 
as such can only calcify ; when it is to become bone, a 


476 LECTURE XIX. 


transformation of its tissue must take place, the chon- 
drine-containing basis-substance must become converted 
into a gelatine-yielding intercellular substance. 

I have, moreover, gentlemen, made a series of prepa- 
rations from ricketty bones for you—on the one hand, — 
because rickets above all offers an especially favourable 
opportunity for obtaining an insight into several processes 
of the normal growth of bone, which in other cases are 
obscured by the presence of calcareous salts—and on the 
other hand, because you will thus form some idea of the 
peculiarity of this process, as such. 

Rhachitis, has, as you are aware, by more accurate 
investigation been shown to consist not in a process of 
softening in the old bone, as it had previously generally 
been considered to be, but in the non-solidification of the 
fresh layers as they form ; the old layers being consumed 
by the normally progressive formation of medullary cavi- 
ties, and the new ones remaining soft, the bone becomes 
brittle. But besides this essential feature of the non- 
occurrence of calcification in the parts, there is displayed 
also a certain irregularity in growth, so that stages in the 
development of bone which, when the formation is nor- 
mal, ought to set in late, set in at a very early period. 
In normal growth, the pointed processes, in which shape 
the calcareous salts shoot up into the cartilage, form, along 
the margin of calcification, such a completely straight line, 
that it should almost be described as mathematically 
regular. This condition ceases to obtain in rickets, and 
the more so, the greater the severity of the case ; inter- 
ruptions occur in such a way, that in some places the 
cartilage still reaches a long way down, whilst in others 
the calcification has mounted up to a considerable height. 
These uncalcified parts sometimes become so completely 
separated from one another, that they remain forming 
specks of cartilage in the midst of the bone, and sur- 





RICKETS. | 477 


rounded on all sides by it—and that cartilage is still 
found at points where the bone ought long since to have 
become transformed into medullary tissue. The farther 
the process advances, the more, however, do we also meet 
with isolated, scattered masses of lime in the cartilage, in 
many instances to such a degree, that the whole of the 
cartilage on section appears dotted with white points. The 
irregularity of the process is further shown in this, that 
whilst in the normal course of things the medullary spaces 
should begin to form only at a short distance behind the 
margin of calcifiation (Fig. 126), they here exceed these 
limits, and in many cases a series of connective cavities 
extends far beyond the border of calcification, which are 
filled with a soft, slightly fibrous tissue, and besides have 
vessels’ running up into them. Medullary spaces and 
vessels are therefore met with, where normally and pro- 
perly not a single medullary cell, and scarcely a single 
vessel ought to be found. 

In this manner there may at all times be found side by 
side in the parts, where the process has attained its height, 
a whole series of different histological conditions. Whilst 
in other cases we find at a certain definite point cartilage, 
at another calcification, at a third, bone, or medullary 
tissue, here everything lies in the greatest confusion ; in 
one place, medullary tissue, above it osteoid tissue, or 
bone, by its side calcified cartilage, and below it, perhaps, 
cartilage still retaining its original condition. The whole 
of the rhachitic portion of the diaphysal cartilage—and it 
may extend for a considerable distance—of course acquires 
no real firmness, and this is one of the chief causes of the 
liability to distortion, which ricketty bones exhibit, not 
in the continuity of the diaphyses, but at the articular 
ends. This is in many cases extremely considerable and 
is the sole cause of many a deformity, as, for example, 
in the thorax. The curvatures in the continuity of the 


478 LECTURE XIX. 


bones are always infractions,* those of the epiphyses are 

due to the proliferation of the cartilage and constitute 

simple inflexions ; and it is easy to conceive that parts, 

which are so entirely deprived of their regular develop- 

ment (as they are in rickets), and ought, properly, to be 
densely impregnated with calcareous salts, must retain 
great mobility. 


Frey 133. 


c 
YGEPES 
Yu E (Ge lan: 




















©) Hil) Wi Di Cc 










CE 








YM. 


™m 


Fig. 188. Vertical section of cartilage from the diaphysis of a ricketty, growing 
tibia from a child two years old. A large conical process of medullary tissue, send- 
ing out a lateral band on the left side, extends from m up into the cartilage ; it con- 
sists of fibrous basis-substance with spindle-shaped cells. At the circumference, at 
c, ¢, c the cartilage in a state of proliferation with large cells and groups of cells; 
at c’, c’ commencing thickening and internal indentation of the cartilage-capsules 
which at 0, 0 coalesce and form osteoid tissue. 300 diameters. 


* By infraction I understand an incomplete fracture (solution of continuity) within 
the periosteum, which remains intact.—From a MS. Note by the Author. 





RICKETTY CARTILAGE. 479 


The enlargement and multiplication of the individual 
cells takes place in the same manner, as in the cases we 
have already considered ; but inasmuch as at a later 
period individual parts in the cartilages, that properly 
ought to have become bone, do not calcify, and especially 
a formation of medullary spaces often takes place a long 
way up above the border of calcification—in many of 
these rhachitic parts the whole history of the develop- 
ment of bone is clearly revealed in a connected form. 
Large and often very vascular conical processes of 
fibrous medullary tissue are seen extending upwards from 
the bone into the cartilage, and it may be very distinctly 
perceived, that these processes do not force their way 
into the cartilage from without, but that they owe their 
origin to a fibrillation of the intercellular substance of the 
cartilage itself. Itis around them chiefly that the osteoid 
transformation of cartilage also can best be seen, and 
particularly that the gradual conversion of a cartilage- 
corpuscle into a bone-corpusele can very distinctly be 
witnessed. Out of the cartilage-corpuscle which has a 
moderately thick capsular membrane, arises a structure, 
provided with a capsule continually increasing in thick- 
ness, within which the space for the cell constantly 
grows smaller, and which, when it has attained a certain 
degree of thickness, acquires indentations on its inner wall, 
like the so-called dotted canals of vegetable cells. Such 
is the mode in which the first rudiments of the bone-cor- 
puscle are traced, after which a fusion of the capsule with 
the basis-substance very generally ensues, and with the 
production of anastomosing processes from the cells the 
formation of the bone-corpuscle is completed. At times 
isolated osteoid cartilage-corpuscles calcify alone without 
the occurrence of any fusion ; and whilst between them 
lies the ordinary intercellular substance of cartilage, the 
capsules of the osteoid corpuscles fill themselves com- 


4 


480 LECTURE XIX. 


pletely with calcareous salts. In other places on the con- 
trary the fusion of the capsules with the intercellular 
substance takes place very rapidly ; the new intercellular 
substance formed by this fusion assumes a coarsely fibrous 
appearance, and in the place of several groups of carti- 
lage-cells we see a fibrous mass, containing Jagged osse- 
ous (bone-), or osteoid corpuscles. There is therefore no 
sharply defined boundary in the tissue, but the condensed 
or fibrous substance, which surrounds the jagged bodies, 
is directly continuous with the translucent substance 
which holds the cartilage together. Hssentially, however, 
it is the same structure.* 

This isolated transformation of single cartilage-cells 
into bone corpuscles is obviously of the greatest impor- 





Fig. 134. Insular ossification in ricketty diaphysal cartilage. ¢, c. Ordinary 
growing (proliferating) cartilage, c’, increasing thickening of the capsules with for- 
mation of an indented cavity (eased cartilage-cells), co’, calcification of similar, 
still isolated cartilage-cells, co, commencing fusion of the capsules of calcified carti- 


lage-cells, 0, osseous substance. 300 diameters. (Cf. Archiv. f. path. Anat., Vol. 
XIV., Plate I. 


*The following section, including the history of the formation of callus, has been 


transferred to this place from the next lecture, inasmuch as a better understanding 
of it is thus insured. 

















OSSIFICATION IN CARTILAGE, 481 


tance to the cellular theory in general. In this speci- 
men (Fig. 134) the whole series of these processes is 
seen at a glance. Where the completely ossified por- 
tion, in which the bone-corpuscles are developed with 
perfect regularity, adjoins the cartilage, you see a zone 
where the conversion of cartilage-corpuscles into perfect 
osseous substance may be viewed within the limits of a 
very short space. At the point of transition a number 
of corpuscles are found lying close to one another like 
hazel-nuts—distinguished from ordinary cartilage-cor- 
puscles by their dark contours, hard appearance, and 
unusually great brilliancy, and enclosing in a small, 
indented cavity a little cell; these little cells are the 
still isolated* bone-corpuscles with calcified capsules 
which they have retained from that earlier period in 
their existence when they were cartilage-cells. It is 
especially important that you should see these bodies 
thus isolated—in situ, in order that you may compre- 
hend those other processes, in which in bone the terri- 
toriest belonging to the bone-cells fall out (p. 462, Fig. 
129). When an object of this kind has once been accu- 
rately examined, it is impossible that doubts can any 
longer arise as to whether cartilage-cells can become 
bone-corpuscles, and I cannot conceive how it is that 
even the most recent (and those very careful) observers 
still start the question, whether bone-corpuscles are not 
in all cases structures obtained by a circuitous route, and 
not directly produced from cartilage-corpuscles. It is 


* Tsolated, because their capsules have not yet become fused with the basis-sub- 
stance.—From a MS. Note by the Author. 

+ In bone formed directly (i. e., without the intervention of medullary tissue) out 
of cartilage, the territories of the bone-cells correspond to the cartilage-capsules. 
But when bone is developed out of any other tissue, the limits of these territories 
cannot be distinguished at all during growth, and it is only when gaps arise (through 
disease) in the bone around the bone-cells that these limits are defined.—From a 
MS. Note by the Author. 


_ 31 


489 LECTURE XIX. 


no doubt true, that in the case of the normal growth in 
length of bone most of the bone-corpuscles do not directly 
proceed from cartilage-corpuscles, but are immediately 
derived from marrow-cells and only mediately from 
cartilage-cells ; but it is just as true that cartilage-cells — 
also can be transformed straightway into bone-cor- 
puscles. It is now a long time since I called attention 
to one spot in particular, where the conversion of carti- 
lage into osteoid tissue can be very distinctly viewed, 
namely at the points of transition from cartilage to peri- 
chondrium in the neighbourhood of the border of calcifi- 
cation of growing bones. Here the boundaries between 
the different forms of tissue are completely obliterated, 
and all sorts of transitions between round (cartilaginous) 
and jagged (osteoid) cells are seen. 

The next preparations have reference to the patholo- 
gical new formation of bone, or, if you will, to the physio- 
logical formation of callus. They are derived from a 
very recent fracture of the ribs, around which a thick 
mass of callus has heen deposited. In reference to this 
process I will add a few words, as it is one that has been 
much discussed and is very important in a surgical point 
of view. : 

You have seen from what I have just been describing 
to you, that there are several ways in which the new 
formation of bone is effected, and that the old supposi- 
tion that either the one or the other mode must be 
considered as the only prevailing one, is incorrect. 
The pre-existence of cartilage is by no means necessary 
for the formation of bone ; on the contrary, an osteoid 
substance is very frequently formed by a direct sclerosis 
in connective tissue, nay, ossification is thus really more 
easily effected than when it takes place in real cartilage. 
We see also by the history of the theories concerning 
callus, that the endeavour to show that it is always 











FORMATION OF CALLUS AFTER FRACTURE, 483 


developed in the same way or out of the same substance 
(e. g. extravasated blood, periosteum, medullary tissue, 
exuded fluids, etc.) has proved the greatest obstacle to 
the true perception of the real. state of things, and that 
all have really had right upon their side, inasmuch as 
new bone in fact builds itself up out of the most differ- 
ent materials. Unquestionably, when the case runs a 
very favourable course, that path is chosen in which the 
new formation can be most conveniently effected, and 
it is by far the most convenient way, when the peri- 
osteum produces a very large portion of the whole. 
This takes place in the following manner: the perios- 
teum grows dense towards the edges of the fracture, 
and there gradually swells up, the swelling being of 
such a nature, that separate layers or strata can after- 
wards pretty clearly be distinguished in it. These 
continually become thicker and more numerous, in con- 
sequence of the constant proliferation of the innermost 
parts of the periosteum—and of the formation, by 
means of a multiplication of their cellular elements, of 
new layers, which accumulate between the bone and the 
relatively still normal parts of the periosteum. These 
layers may become cartilage, but it is not necessary, 
nor yet the rule. For we find that, in the greater num- 
ber of favourable cases of fracture, where cartilage is 
produced, not the whole mass of the periosteal callus 
is produced from cartilage, but a greater or less portion 
of it is always formed out of connective tissue. The 
layers of cartilage generally lie next to the bone, whilst 
the farther we proceed outwards, the less does the for- 
mation out of cartilage, and the more a direct transfor- 
mation of connective tissue, prevail. 

The formation of bone is, however, by no means 
restricted to the limits of the periosteum—very com- 
monly it extends beyond them in an outward direction, 


484 LECTURE XIX. 


and often penetrates, in the form of spicula, nodules, 
and protuberances, to a very considerable depth into | 
the neighbouring soft parts. It is self-evident that in 
these cases we have by no means to deal with any proli- 
feration of the periosteum in any outward direction, but 
that an ossifiable tissue arises out of the interstitial con- 
nective tissue of the neighbouring parts. Of this it is 
very easy to convince oneself, because osseous spicula 
are found shooting up in the interstitial tissue of the 
neighbouring muscles. In the preparation from the 
fractured ribs places are still to be found in the external 
parts, where fat has been included 
in the ossification. It cannot be said 
therefore that the formation of callus 
around fractured parts is altogether 
a periosteal formation ; in all cases 
where it takes place with a certain 
abundance, it transgresses the limits 
of the periosteum, and invades the 
connective tissue of the surrounding 
soft parts. 

There is a second kind of eallus- 
formation completely different to 
this —that namely, which takes 
place in the midst of the bone from 
the medullary tissue. 

At the moment when the bone in a case of fracture 





Fig. 135. Transverse fracture of the humerus with formation of callus, about 
fourteen days old. On the outside is seen the porous capsule of the callus pro- 
duced from the periosteum and soft parts, the innermost layer on the right side 
being still cartilaginous. On the left lies detached a fragment shivered off from 
the cortex of the bone. The two fractured ends are connected by a (dark-red) 
fibrinous layer of hemorrhagic origin; the medulla on both sides is very dark 
(owing to hyperemia and extravasation), in the lower fragment several porous 


islands of callus are seen which have been produced by the ossification of the 
medulla. 


FORMATION OF CALLUS AFTER FRACTURE. 485 


is shivered, a number of little medullary spaces are 
naturally opened. In the neighbourhood of these, the 
still closed medullary spaces are seen nearly invariably, 
when matters follow a regular course, to become filled 
with callus, new lamelle of bone attaching themselves to 
the internal surface of the osseus trabeculee which bound 
the spaces, just as in the ordinary growth of bone in 
thickness, the originally pumicestone-like layers-become 
compact by the deposition of concentric lamelle. In 
this manner it happens, that after some time a larger 
or smaller new layer of bone is found, filling up the end of 
the medullary canal of each fragment, so as to occasion its 
occlusion. This is a kind of a new formation which has 
nothing in common with the former one, as far as their 
starting points are concerned, but has its origin in quite 
another tissue, and is altogether different in its palpable 
result, inasmuch as it produces, within the confines of 
its own bone, a condensation of that portion of the mar- 
row which lies in the immediate vicinity of the fracture. 
Even in cases where the ends of the bones perfectly co- 
incide, an internal formation of bone such as I have 
described takes place in the medullary canal of each 
fragment, producing its occlision. 

These two kinds are the usual and normal ones, 
Around the two fractured ends the swelling takes place, 
in the interior, the condensation. Gradually, in pro- 
portion as the extravasated blood is absorbed—the new 
masses of tissue which have been developed between 
the broken ends draw nearer to one another, and round 
about the fracture forms a bridge- or capsule-like com- 
munication by means of the ossification of the soft parts. 
There is therefore.but little reason to ask whether the 
callus proceeds from free exuded or extravasated mat- 
ter. No doubt an extravasation takes place in the first 
instance into the space between the fractured ends, but 


486 LECTURE XIX. 


the extravasated blood is generally pretty completely 
reabsorbed, and it contributes comparatively but very 
little to the real formation of the subsequent uniting 
media. 


We discussed, gentlemen, last time, the chief points 
in the history of new-formations. You remember that, 
according to our ideas, every kind of new-formation— 
inasmuch as it has its origin in pre-existing cellular ele- 
ments and takes their place—must necessarily be 
connected with a change in the given part of the body. 
It is no longer possible to defend an hypothesis such as 
that which, based upon the supposed existence of plastic 
matters, was formerly maintained, namely, that a sub- 
stance was deposited between and upon the existing 
elements of the body, which produced a new tissue out 
of itself and thus represented a clear accession to the 
body. If it is true that every new-formation proceeds 
from definite elements, and that usually divisions of the 
cells are the means by which the new-formation is pro- 
duced, it becomes of course self-evident that where a 
new-formation takes place, certain histological elements of 
the body must generally also cease to exist. Kiven a cell, 
which simply divides and out of itself produces two new 
cells like itself, thereby ceases to exist, even though 
the whole result is only the apparent apposition of a 
cell. This holds good for all kinds of new-formations, 
both for benignant as well as for malignant ones, and it 
may therefore in a certain sense be said, that every kind 
of new-formation is really destructive, and that it destroys 
something of what previously existed. But we are, as it 
is well-known, accustomed to judge of destruction 
according to the more obvious effects produced, and 
when we speak of destructive formations, we do not so 
much mean those, in which the result of the new-forma- 











HOMOLOGOUS AND HETEROLOGOUS NEW FORMATION. 487 


tion is analogous to the old one, as some product or 
other deviating more or less from the original type of 
the part. This is the point of view to which I have 
already (p. 93) directed your attention when treating of 
the classification of pathological new-formations. By it 
is a reason, sensible and in correspondence with the facts, 
afforded for the separation of all. new-formations into 
homologous and heterologous ones. 

Heterologous we may call not only malignant, degene- 
rative neoplasms, but we must also thus designate every 
tissue which deviates from the recognized type of the 
part, whilst we should call all that homologous, which, 
although new-formed, still. reproduces the type of its 
parent soil. We find, for example, that the so ex- 
tremely common form of uterine tumour, which has 
been designated fibrous or fibroid, has in every respect 
the same structure that the walls of the ‘ hypertro- 
phied” uterus have, inasmuch as it consists not only of 
fibrous connective tissue and vessels, but also of muscu- 
lar fibre-cells. The tumour may, as it is well-known, 
become so large, as not only to embarrass the uterus 
in all its functions in an extreme degree, but also to 
exercise through pressure the most injurious influence 
upon the neighbouring parts... In spite of this, it must 
always be considered an homologous structure. On the 
other hand we cannot help employing the term hetero- 
logous formation, as soon as, by means of a process 
which at first seems to represent a simple multiplication 
of the parts, a result is obtained which is essentially 
different from the original condition of the spot. A 
catarrh for example in its simple form may be attended 
by a multiplication of the cellular elements on the sur- 
face of the mucous membrane, without the new cells’ 
being essentially different from the pre-existing ones. 
Thus I brought along with me for you last time a vagina 


488 LECTURE XIX. 


with very marked leucorrhcea. You saw there no 
doubt that the cells in leucorrhcea very closely resemble 
those of epithelium of the part, although they no longer 
entirely retain the typical form of pavement epithelium. 
The less, however, they approach in their development 
the typical forms of the epithelium of the part, the more 
incapable do they become of performing their functions. 
They are moveable upon a surface, to which they ought 
properly to adhere, they flow down* and produce re- 
sults which are incompatible with the integrity of the 
parts. 

In the narrower sense of the word heterologous new- 
formations are no doubt alone destructive. The homo- 
logous ones may accidentally bec ome veryinjurious, but. 
still they do not possess what can properly be called a 
destructive (in the unscientific and traditional sense of 
the word), or malignant character. On the other hand 
every kind of heterologous formation, whenever it has 
not its seat in the entirely superficial parts, has a certain 
degree of malignity clinging to it. And even superficial 
affections, though entirely confined to the most external 
layers of epithelium, may gradually exercise a very 
prejudicial influence. Let us only reflect what happens 
when a large surface of mucous membrane continually 
secretes, and heterologous products are constantly engen- 
dered upon it which do not become persistent epithelium, 
but continually keep flowing down from the surface of 
the mucous membrane. In such a case, in addition to 
the blennorrhcea (and its consequences, anzemia, neural- 
gia, etc.), we find erosions. 

It seems to me important that I should bring before 
you a definite example of the mode in which destruction 
in its more obvious forms is effected, in order that you 


* Karappéw (catarrh). 





LUXURIATION. 489 


may see how it leads to ulceration and to the formation 
of cavities in the interior of parts. It does indeed 
appear like a contradiction to say that a process, which 
produces new elements, destroys, but this contradiction 
nevertheless is merely a seeming one. If you imagine in 
a part, which had previously been firm, a new-formation 
to arise of which the individual constituents are loose 
and easily moveable one upon the other, the process 
will of course always be attended by a very important 
change in the usefulness of the part. The simple con- 
version of bone into medullary tissue (pp. 452, 453) 
may become the cause of great fragility in the bones, 
and osteomalacia [mollities ossium] essentially depends 
upon nothing else than the conversion of compact osse- 
ous substance into medullary tissue. An _ excessive 
formation of medullary spaces gradually advances from 
the interior of the bone towards the surface, deprives 
the bone of its firmness, gives rise to a tissue in itself 
quite normal, but of no service in maintaining the 
necessary firmness of the parts, and thus in some sort 
inevitably leads to a loss of cohesion. Marrow is an 
extraordinarily soft tissue, which in those conditions, 
where it is red and rich in cell, or atrophied and gela- 
tinous, becomes nearly fluid. From marrow to perfectly 
fluid tissues is only a short step, and the boundaries 
separating marrow and pus cannot in many places be 
assigned with any degree of certainty. Pus is in our 
eyes a young tissue, in which, amidst the rapid develop- 
ment of cells, all solid intercellular substance is gra- 
dually dissolved: A single connective-tissue cell may in 
an extremely short space of time produce some dozens 
of pus-cells, for the development of pus follows an ex- 
tremely hurried course. But the result is of no service 
to the body, proliferation becomes luxuriation. Suppura- 


. tion is a pure process of luxuriation, by means of which 


490 LECTURE XIX. 


superfluous parts are produced, which do not acquire 
that degree of consolidation, or permanent connection 
with one another and with the neighbouring parts, which 
is necessary for the existence of the body. 

If now in the next place we investigate the history of 
suppuration, we immediately discover that we must dis- 
tinguish two different modes of pus-formation, according 
namely as the pus proceeds from tissues of the first two 
kinds mentioned in our classification (p. 55), 

i. e., from epithelium or from connective Fic. 186. 
tissue. Whether there are also forms of mn 
suppuration proceeding from a tissue of the E 
third class, from muscles, nerves, vessels, 
etc., is at least doubtful, because of course 
the elements of connective tissue which 
enter into the composition of the larger 
vessels, the muscles and the nerves, must 
be eliminated from the really muscular, ner- 
vous and vascular (capillary) elements. With this reser- 
vation we can for the present only maintain the possibil- 
ity of two modes of pus-formation. 

As long as the pus is formed out of epithelium, it is 
naturally produced without any considerable loss of sub- 
stance and without ulceration. But this is in every 
instance the case, where pus is produced in connective 
tissue. The real state of the matter therefore is exactly 
the reverse of what it was previously imagined to be, 
when a solvent property was ascribed to pus. Pus ts not 
the dissolving, but the dissolved, 1. e., the transformed, tissue. 
A part becomes soft, and liquefies whilst suppurating, 
but it is not the pus which occasions this softening, on 





1 


, 


Fig. 136. Interstitial purulent inflammation of muscle in a& puerperal woman. 
m, m- Primitive muscular fibres. 4, 4. Development of pus-corpuscies by means of 
the proliferation of the corpuscles of the interstitial connective tissue. 280 dia- 
meters. 


EPITHELIAL SUPPURATION. 491 


the contrary, it is the pus which is produced as the result 


' of the proliferation of the tissue. 


The development of pus we daily see upon different 
surfaces, both on the skin, and on mucous and serous 
membranes. We can observe its development most 
surely where stratified epithelium naturally exists. If 
you follow the development of pus upon the skin, when 
the process is unaccompanied by ulceration, you will 
constantly see that the suppuration proceeds from the 
rete Malpighi. It consists in a growth and develop- 
ment of new cells in this part of the cuticle. In pro- 
portion as these cells proliferate, a separation of the 
harder layers of the epidermis ensues, and they are lifted 
up in the form of a vesicle or pustule. The place where 
the suppuration chiefly occurs corresponds to the super- 
ficial layers of the rete, which are already in process 
of conversion into epithelium ; if the membrane of the 
vesicle be stripped off, these (layers) usually adhere to 
the epidermis and are stripped off with it. In the 
deeper layers we may watch how the cellular elements, 
which originally have only a single nuclei, divide, how 
the nuclei become more abundant, and single cells have 
their places taken by several, which in their turn again 
provide themselves with dividing nuclei. Here too: 
people have generally helped themselves out of the 
difficulty by assuming that in the first instance an exu- 
dation was poured out, which produced the pus in itself, 
and this is the reason why, as you well know, most 
investigators into the development of pus especially se- 
lected fluids which were secreted from injured surfaces. 
It was very conceivable that, as long as no doubts were 
entertained with regard to the discontinuous formation 
of cells, the young cells should without more ado be 
looked upon as independent new-formations, and that 
the notion should be entertained that germs arose in the 


499 LECTURE XIX. 


exuded fluids, and gradually becoming more numerous, 
supplied the pus. But the matter is on this wise, that, 
the longer the suppuration lasts, the more certainly is 
one series of cells after the other in the rete involved 
in the process of proliferation, and that, whilst the — 
vesicle is rising up, the quantity of the cells which grow 
into its cavity is constantly becoming greater. When 
a variolous pustule forms, there is at first only a drop 
of clear fluid present, but nothing arises in it ; it only 
loosens the neighbouring parts of the rete Malpighi.. 
Precisely the same is the case with mucous membranes. 
There is not a single mucous membrane which may not 
under certain circumstances furnish puriform elements. 
But here too a certain difference always presents itself. 
A mucous membrane is all the more in a condition to 
produce pus without ulceration, the more completely the 
epithelium it possesses is stratified. All mucous mem- 
branes with a single layer of cylindrical epithelium (intes- 
tines),* are much less adapted for the production of pus ; 
that which is produced on them, even though it have 
quite the appearance of pus, frequently turns out upon 
close examination to be only epithelium. The intestinal 
mucous membrane, especially that of the small intestine, 
scarcely ever produces pus without ulceration. The 
mucous membrane of the uterus, and of the fallopian 
tubes, though it is frequently covered with a thick mass 
of quite a puriform appearance, almost always secretes + 


* In the air passages (nose, larynx, trachea, bronchi) we commonly find several 
layers of cylindrical epithelium lying one above the other.—From a MS. Note by the 
Author. 

+ Secrete in this and similar places does not of course mean to separate from the 
blood, but from the tissue itself, whose elements (cells) are separated (detached) at 
the surface, and, when mixed with the serous effusion from the blood, removed. 
The detachment of the cells is effected sometimes by means of the fluid which trans- 
udes from the blood, sometimes by the continual growth of a succession of new cells 
beneath them, and sometimes in consequence of their own round form. In desqua- 
mation of the cuticle the second of these methods, in several forms of catarrh the 











RELATION OF PUS AND MUCUS TO EPITHELIUM. 493 


epithelial cells only, whilst on the other mucous mem- 
branes, as for example on that of the urethra, we see 
enormous quantities of pus secreted, as in gonorrhoea 
(Fig. 63) without even the slightest ulceration being pre- 
sent on the surface. This depends essentially upon the 
presence of several strata of cells, the upper forming a 
kind of protection to the deeper ones, of which the pro- 
liferation is thus for a time secured. The pus is at last 
either borne away by the production of new masses of 
pus beneath it, or there occurs simultaneously a transuda- 
tion of fluid, which removes the pus-cells from the surface, 
just as in the secretion of semen the epithelial elements 
of the seminal tubules furnish the spermatozoa, and in 
addition a fluid transudes which sweeps them away. But 
the spermatozoa do not arise in the fluid—this is only the 
vehicle for their onward movement. In this manner we 
frequently see fluid exude on the surface of the body, 
without our being able to regard it as a cytoblastema. 
If a proliferation of epithelium simultaneously takes place 
upon the surface, the elements detached by the transuded 
fluid will also be found to consist of nothing but prolife- 
rating epithelium. 

If now pus-, mucus- and epithelial cells be compared with 
one another, it appears that there certainly does exist a se- 
ries of transitional forms, or intermediate stages, between 
pus-corpuscles and the ordinary epithelial structures. 
By the side of perfectly formed pus-corpuscles, provided 
with several nuclei, are very commonly found somewhat 
larger, round, granular cells with single nuclei, the so- 
called mucus-corpuscles (Fig. 11 B) ; a little further on 
we see perhaps still larger cells of a typical form and with 
single, large nuclei, and these we call epithelial cells. 
But the epithelial cells are flat, angular, or cylindrical, 


third, on many serous membranes, the first, is the one pursued. Any two, or all 
three of them, however, may of course coincide.—Hrom a MS. Note by the Author. 


494 LECTURE XIX. 


whilst mucus- and pus-corpuscles under all circumstances 
remain round. Even from this circumstance may be 
derived an explanation of the fact that, whilst the epithe- 
lial cells, which cover, and are in close apposition to, one 
another, acquire a certain firmness of cohesion, mucus- 
and pus-corpuscles which lie but loosely one against the 
other, and are of a spherical shape, retain a great degree 
of mobility and are easily displaced. 

It has been said before now that mucus-corpuscles are 
nothing more than young epithelium ; another step and 
pus-corpuscles would be nothing more than young mucus- 
corpuscles. This is a somewhat erroneous notion. It 
cannot be maintained that a cell, which up to the point 
when it becomes a so-called mucus corpuscle has pre- 
served its form as a spherical body, is still in a condition 
to assume the typical form of the epithelium, which ought 
to exist in the part ; and just as little can it be said that 
a pus-corpuscle, after it has developed itself in the regu- 
lar manner, is capable of again entering upon a course of 
development calculated to produce a relatively perma- 
nent element of the body. The cells, in which the deve- 
lopment of epithelial, mucus-, and pus-cells originates, 
are young forms, but they are not pus-corpuscles. In 
pus every new cell at a very early period sets about 
dividing its nucleus ; after a short time the division of 
the nucleus reaches a high pitch, without any further 
growth on the part of the cell. In mucus the cells are 
wont merely to grow, and in some instances to become 
very large, but they do not pass certain limits, and above 
all they do not assume any typical form. In epithelium, 
on the contrary, the elements begin even at a very early 
period, to assume their particular form, for ‘‘ what is to 
become a hook, right early gets a crook.” The very 
youngest elements however, which are found in patholo- 
gical conditions, cannot be called epithelial cells, or at 





SUPPURATION IN CONNECTIVE TISSUE. 495 


least they have as yet nothing typical about them, but 
are indifferent formative cells, which might also become 
mucus- or pus-corpuscles. _Pus-, mucus- and epithelial 
cells are therefore pathologically equivalent parts which 
may indeed replace one another, but cannot perform 
each other’s functions. 

Even from this it follows that the distinction which it 
has been sought to establish between mucus- and pus- 
corpuscles, and for the discovery of which. prizes were 
proposed in the last century, really could not be found 
out, and that the ‘‘ tests’ could never be otherwise than 
insufficient, inasmuch as the cells developed upon mucous 
membranes do not always possess a purely purulent, 
purely mucous, or purely epithelial character, but on the 
contrary in a great majority of cases a mixed condition 
exists. Nearly always, when a catarrhal process deve- 
lopes itself upon a large mucous surface, as, for example, 
in the urinary passages, quantities of puriform matter are 
produced, but its production is: confined within certain 
limits, beyond which only mucus is secreted, and the 
secretion of mucus also at some point changes into a 
formation of epithelium. This mode of suppuration must 
of course always have for its result, that, in places where 
it reaches a certain height, the natural coverings of the 
surface do not attain their full development, or that, 
where they possess a certain degree of solubility, they 
are removed and destroyed. A pustule on the skin 
destroys the epidermis, and so far we may assign a 
degenerative character to these forms of suppuration 
also. 

But degeneration in the usual sense of the word, only 
occurs when deeper parts are attacked. This more deeply 
seated pus-formation regularly takes place in the connec- 
tive tissue. In it there first occurs an enlargement of the 
cells (connective-tissue corpuscles), the nuclei divide and 


496 LECTURE XIX. 


for some time multiply excessively. The first stage is 
then very soon followed by divisions of the cells them- 
selves. Round about the irritated parts, where before 
single cells lay, pairs or groups of cells are subsequently 
found, out of which a new-formation of an homologous 
kind (connective tissue) usually constructs itself. More 
in the interior on the contrary, where the cells were 
early abundantly filled with nuclei, heaps of little cells 
soon appear, which at first 








still preserve the direction Fig, 137. 
and forms of the previous 0D 0 5¢ 

; ‘ Oz O= Ore = 
connective-tissue corpus- ¢? 3% 


il 


cles. Somewhat later we 
find here roundish collec- 
tions, or diffuse ‘‘ infiltra- 
tions,” in which the inter- 
mediate tissue 1s extremely 
scanty and continually liquefies * more and more, in pro- 
liferation of the cells extends. 

If this process takes place beneath a surface which 
does not participate in the morbid change, the layers of 
epithelium are sometimes seen, still perfectly coherent, to 
run over the irritated and somewhat swollen part. The 
outermost layer of the intercellular substance is also often 
long preserved, whilst all the deeper parts of the connec- 
tive tissue are already filled with pus-corpuscles, are 
“infiltrated,” or “‘absceded” + (abscedirt). At last the 


Fig. 137. Purulent granulation from the subcutaneous tissue of a rabbit, round 
about a ligature. a. Connective-tissue corpuscles. 6. Enlargement of the corpus- 
cles with division of the nuclei. ¢. Division of the cells (granulation). d, Develop- 
ment of the pus-corpuscles, 300 diameters. 


* This liquefaction (and the same is true of the liquefaction we have described as 
occurring in bone, p. 465) is a purely chemical process; the collagenous ( gelatine- 
yielding) substance is first transformed into mucus, and then, becoming converted 
into an albuminous fluid, liquefies—From a MS. Note by the Author. 

+ Ie. converted into an abscess.—Zransl. 




















——— inns 


GRANULATION, ULCERATION, 497 


surface gives way, or without giving way is directly 
transformed into a soft, diffluent mass. This mode of 
suppuration gradually yields the so-called granulations 
which always consist of a tissue, where, ina small quan- 
tity of soft intercellular substance, more or less numerous, 
and, at least in the strictly proliferating stage of the 
granulations, round, cellular elements are imbedded. 
The nearer we come to the surface, the more do. the 
cells, which in the deeper parts were mostly uni-nuclea- 
ted, present divisions in their nuclei, and on the extreme 
confines they can no longer be distinguished from pus- 
corpuscles. Then a detachment of the epithelium is 
wont to take place, and finally it may be that the basis- 
substance liquefies and the individual elements are set free. 
If the proliferation continues abundant, the mass keeps 
constantly breaking up, the cells pour themselves out 
upon the surface, and a destruction takes place, which 
makes deeper and deeper inroads into the tissue, and 
throws up more and more of its cells upon the surface. 
This is an weer properly so called. 

According to the common notion, which supposed the 
pus to be derived from some exudation or other, this 
kind of ulceration was not at all easy of comprehension ; 
people always found themselves obliged to assume a 
special kind of transformation in the tissue in addition to 
the suppuration, and at last they went so far as to attri- 
bute a certain chemical solvent power to pus. But by 
surgical experiments the conviction has long since been 
acquired in the most manifold ways that pus has no sol- 
vent power. Bones have been placed in cavities full of 
pus and left there for weeks, and when they were after- 
wards weighed, they had if anything become heavier, 
through the absorption of fluid matters, but no softening 
had been produced excepting that occasioned by decom- 


position. How far the tissue is destroyed by real solu- 
82 


498 LECTURE XIX. 


tion, chiefly depends upon whether the basis-substance 
which surrounds the young cells, becomes completely 
fluid. If it retains a certain degree of consistence, the 
process is confined to the production of granulations, and 
these may just as well proceed from a surface whose © 
continuity is perfect, as from one where there is a breach 
of it. In surgery it is generally assumed that granula- 
tions form upon the walls of the breach occasioned by a 
loss of substance, but in every case they arise directly 
out of the tissue. They are found directly seated upon 
bone without any loss of substance in it having preceded 
them. They are found also in direct contact with the 
cutis under the intact epidermis, and with mucous mem- 
branes. Only in proportion as they become developed, 
do the mucous membranes lose their normal character. 

Every development of the kind gives rise, as it pro- 
ceeds, to separate masses (foci—Heerde) of new tissue, 
just in the same way indeed that growing cartilage 
produces, in the immediate vicinity of the margin of 
ossification, those large groups of cells (Fig. 124), each 
of which corresponds to a single pre-existing cartilage- 
cell. We have in fact to do with a process which finds 
its counterpart in the ordinary phenomena of growth. 
As a cartilage, when it does not calcify, as for example, 
in rickets, at last becomes so moveable that it can no 
longer perform its functions as a supporting structure, 
sO we see everywhere that the firmness of a tissue gra- 
dually disappears through the development of granula- 
tions, and during suppuration. However different there- 
fore these processes of destruction apparently are from the 
processes of growth, at a certain point nevertheless 
__,_ they entirely coincide. There is a stage, when it is im- 

| possible to decide with certainty, whether we have in a 
1 part to deal with simple processes of growth, or with the 
le development of a heteroplastic, destructive form. 








DURATION OF LIFE OF INDIVIDUAL ELEMENTS. 499 


This mode of development, which I have just de- 
scribed to you, is not, however, in any way peculiar. to 
pus alone, but characterizes every heteroplastic forma- 
tion ; the first changes which we have shown to take 
place are found occurring in exactly the same manner in 
heteroplasms of every sort up to the most extreme and 
malignant forms. The first development of cancer, of 
cancroid and of sarcoma exhibits the same stages ; if 

the course of their deve- 
Fra, 138, lopment be traced  suffi- 
“ ciently far back, we at last 


We ><Se\\ always come across a stage 
oe y £ ’ 







Q Os in which, in the younger 
RON AS PASO : bl 
Se GaN and deeper layers, indif- 
c ‘ BN \\ 
ox ferent cells are met with, 
\oi which do not until a later 


period, according to the 
particular nature of the 
irritation to which they are exposed, assume the one or 
the other type. We may therefore, taking new-forma- 
tions in general, consider the history of the greater 
number, and especially of those which principally con- 
sist of cells, from an entirely similar point of view. 
The form of ulceration which is presented by cancer in 
‘ts latest stages, bears so great a resemblance to its sup- 
purative ulceration, that the two things have long since 
been compared, and quite in the olden time a parallel 


Fig. 188. Development of cancer from connective-tissue in carcinoma of the 
breast. «@. Connective-tissue corpuscles, 5, division of the nuclei, ¢, division of the 
cells, d, accumulation of the cells in rows, e, enlargement of the young cells and 
formation of the groups of cells* (foci—Zellenheerde) which fill the alveoli of can- 
cer, f, further enlargement of the cells and the groups. g. The same developmental 
process seen in transverse section, 800 diameters. 


* When these groups of cells fall out, the alveoli (loculi) of cancer appear, the 
relation of the group to the alveolus being the same as that of the bone-cell to the 
lacuna.—From a MS. Note by the Author. 


500 LECTURE XIX. 


was drawn between the eroding form of suppuration, or 
chancre, and the ‘‘suppuration” or sanious ulceration®™ 
(Verjauchung) of cancer. 

But there are essential differences between the indi- 
vidual species of new-formations in consequence of their 
elements’ attaining to very different degrees of develop- 
ment, or to express myself otherwise, in consequence 
of the length of time their elements are calculated to 
last—the average duration of the life of the individual 
elements—being extremely different. We know, that if 
we examine a spot a month after suppuration has taken 
place in it, although the pus is apparently still present, 
we can no longer rely upon finding unaltered pus 
in the collection. Pus which has lain anywhere for 
weeks and months is, strictly speaking, no longer pus, 
but disintegrated matter, débris, dissolving particles of 
pus, which have become altered by fatty degeneration, 
putrefying processes, calcareous deposits and the like. 
On the contrary we find that a cancerous tumour may 
last for months, yet still contain the whole of its ele- 
ments intact. We can therefore positively affirm, that 
a cancer-cell is capable of existing longer than a pus- 
corpuscle, just as we know that the thyroid body exists 
longer than the thymus gland, and that certain organs, 
for example individual parts of the sexual organs, early 
perish in the course of ordinary life, whilst others retain 
their existence throughout the whole of life. So it is 
also with pathological new-formations. At a time when 
certain forms have long since entered upon their course 
of retrogressive metamorphosis, others are just begin- 


* Jauche (sanies) always conveys the idea of decomposition. We call Mist 
jauche the fluid obtained by the maceration of manure. Verjauchung is the pro- 
cess during which the substances are decomposed which subsequently furnish the 
Jauche. The French putrilage is nearly equivalent to Jauche in its pathological 


acceptation, only the latter is rather thinner and more liquid.— From a MS. Note 
by the Author. 





COMPOUND NATURE OF TUMORS. 501 


ning to attain their full development. In the case of 
many new-formations, retrograde metamorphosis begins 
comparatively so early, nay constitutes to such a degree 
what is ordinarily met with, that the best investigators 
have looked upon its different stages as the really 
characteristic ones. In the case of tubercle, for exam- 
ple, we find that the majority of all modern observers 
who have made it their professed study, have taken its 
stage of retrograde metamorphosis for the real typical 
one, and that inferences have hence been drawn with 
regard to the nature of the whole process, which with 
equal right might have been drawn with regard to the 
different stages of the retrograde metamorphosis of pus 
and cancer. 

We are as yet able in the case of very few elements 
to give in numbers with absolute certainty the average 
length of their life. There manifestly exist variations 
similar to those we meet with in normal organs. But 
among all pathological new-formations with fluid inter- 
cellular substance there is not a single one, which is 
able to preserve its existence for any length of time, 
not a single one, whose elements can become permanent 
constituents of the body, or exist as long as the indi- 
vidual. This may no doubt seem doubtful, because 
many forms of malignant tumours subsist for many 
years, and the individual retains them from the time of 
their development until his death, which may perhaps 
occur at a very advanced age. But the tumour as a 
whole must be distinguished from its individual parts. In 
a cancerous tumour which lasts for many years, the 
same elements do not last the whole time, but within 
its limits there occurs a frequently very numerous suc- 
cession of fresh formations. The first development of a 
tumour takes place at a definite point, but its subse- 
quent growth does not consist in the production of a 


a 
+ 
, 


s 


502 LECTURE XIX. 


constant succession of new-formations from this point, 


and in the occurrence there is an intus-susception (ab- _ 


sorption) of material, by means of which the existing 
parts enlarge and so the whole tumour grows. On the 


contrary around the original focus* (Heerd), little new foci 


are formed, which increasing in size, group themselves 
around the first, and so gradually give rise to a continually 
progressing enlargement of the existing tuber.f If the 
tuber is seated on the surface, we find on section a semicir- 
cular zone of the most recently formed matter, at its 
periphery ; if it is in the middle of an organ, the newly 
apposed foci form a spherical cortex around the older 
centre. If we examine a tumour after it has existed 
perhaps a year, it usually turns out that the elements first 
formed no longer exist in the centre. There we find the 
elements disintegrating, dissolved by fatty changes. If 
the tumour is seated on a surface, it often presents in 
the centre of its most prominent part a navel-shaped 
depression, and the portions immediately under this 
display a dense cicatrix which no longer bears the ori- 
ginal character of the new-formation. These retrograde 
forms I have described as occurring in cancer, especially 
in the liver, lungs and intestines, where they are not 
unfrequently met with, and can readily be demon- 
strated. 

It is always possible to convince oneself, that, what 1s 
called a tumour, constitutes a conglomerate mass, often 
extraordinarily large, made up of a number of little mil- 
ary foct (lobules), of which every single one must be 
referred to a single or a few parent elements. Inas- 
much as the formations progress in this manner, no 


* Focus here signifies the first rudiment of a tumour, produced by the prolifera- 
tion of a limited group of cells. See note on Heerd, p. 881.—From a MS. Note by 
the Author. 


+ Tuber = tuberous tumour. See note, p. 471. 


TRANSFERRENCE OF INFECTION. - J808 


matter whether they consist of pus, tubercle or cancer, 
new young zones are being constantly added on to the 


old ones, and we may, it we intend to trace the course 


of development, calculate with great certainty upon 
always finding the young parts at the extreme circum- 
ference, the old ones always in the centre. But the 
zone produced at the latest period of the disease extends to 
a considerable distance beyond the zone of degeneration 
that can be discerned by the naked eye. If we examine 
any proliferating tumour of a cellular character, we 
often find, three to five lines beyond its apparent limits, 
the tissues already in a state of disease, and oxhibitibe 
the first traces of a new zone. This is the chief source 
of local recurrence after extirpation, for it proceeds 
from the zone that cannot be detected by the naked eye, 
beginning to grow in consequence of the increased sup- 
ply of nutritive material which results from the removal 
of the original tumour. No new deposit from the blood 
takes place there, but the new-formed germs, which 
already lie in the neighbouring tissue, run through their 
further development in the same manner that it would 
otherwise have taken place, or perhaps even still more 
quickly. 

This fact I regard as extremely important, because it 
shows us that all these formations have essentially a 
contagious character. As long as it was imagined that 
the mass once formed increased only by the growth of 
its constituents, it would of course look as if all one had 
to do for the purpose of getting rid of it was merely to 
cut off from the tumour all further supply of material. 
But there is manifestly a contagious matter formed in 
the tumour itself, and when the cells, which are in its 
immediate neighbourhood and are connected by anasto- 
moses with the diseased cells, likewise enter upon the 
heterologous proliferation, it is impossible, I think, to 


504 LECTURE XIX. 


come to any other conclusion in the matter, than that 
the degeneration cf the neighbouring parts arises in 
precisely the same manner as that of the nearest lym-- 
phatic glands which lie in the course of the stream of 
lymph which proceeds from the diseased part. The 
more anastomoses the parts possess, the more readily do 
they become diseased, and vice versd. In cartilage ma- 
lignant affections are so rare, that it is usually assumed 
to be altogether insusceptible of them. Thus in a joint 
the cartilaginous investment alone is sometimes found 
intact, whilst everything else has been destroyed. Thus 
too we see that fibrous parts which are rich in elastic 
elements, are very little disposed to become diseased by 
contagion. On the other hand, the softer a basis-sub- 
stance is and the better the conveyance can take place, 
the more certainly we may expect, that, when occasion 
offers, new foci of disease will arise in the part. I have 
therefore come to the conclusion—the only one I think 
the facts warrant—that the infection is directly trans- 
ferred by the means of the morbid juices from the 
original seat of the disease to the anastomosing ele- 
ments in the neighbourhood, without the intervention of 
vessels and nerves. The nerves are indeed often the 
best conductors for the propagation of contagious new- 
formations, only not as nerves, but as parts with soft in- 
terstitial tissue. 

Here we have the importance of the anastomosing cel- 
lular elements of tissues, and the value of the cellular 
theory most clearly exhibited, and, when once we have 
become acquainted with this mode of conduction, we are 
afterwards able with a certain degree of probability to 
foresee in what direction, in parts possessing this means 
of conveyance, the disease will extend, and where finally 
the greater or less danger lies. It has hitherto been im- 
possible to prove whether the infection of remote parts 





-PARASITISM. 503 


is effected by the conveyance of juices, in the same way 
that the infection of neighbouring parts is, and especially 
whether the blood takes up anything noxious from the 
diseased spot and conveys it to a distant place. I must 
confess that I am acquainted with no sufficiently con- 
vincing facts bearing upon the matter, and must still 
allow it to be possible that the diffusion by means of ves- 
sels may depend upon a dissemination of cells from the 
tumours themselves. There are, however, many facts, 
which speak but little in favour of the infection’s taking 
place by means of really detached cells, for example, the 
circumstance that certain processes advance in a direc- 
tion contrary to that of the current of lymph, so that 
after a cancer of the breast, disease of the liver takes 
place whilst the lung remains unaffected. Here it seems 
pretty probable tbat juices are taken up, which occasion 
a further propagation (p. 254). . 

Allow me still to add a few words upon a subject which 
can here be dispatched off hand, namely, the so-called 
parasitism of new-formations. 

It is self-evident, that the view taken of parasitism by 
the old writers who held it to be applicable to a large 
proportion of new-formations, is completely borne out by 
facts, and that in reality every new-formation which con- 
tributes to the body no serviceable structures, must be 
regarded as a parasitical element in the body. Only bear 
in mind that the idea conveyed by parasitism does not 
differ from that conveyed by the autonomy of every part 
of the body excepting in degree, and that every single 
epithelial and muscular fibre-cell leads a sort of parasiti- 
cal existence in relation to the rest of the body, just as 
much as every individual cell in a tree has in relation to 
the others a special existence, appertaining to itself alone, 
and deprives the remaining cells of certain matters. Pa- 
rasitism in a narrower sense of the word, develops itself 


506 LECTURE XIX. 


out of this idea of the independence of individual parts. 
As long as the requirements of the remaining parts de- 
mand the existence of a part, as long as this part is in 
any way useful to the other parts, so long will it not be 


termed a parasite ; but it becomes so from the moment — 


that it becomes foreign or injurious to the body. The 
epithet, parasitical, must therefore not be restricted to a 
single class of tumours, but applies to all heteroplastic 
forms, which do not in the course of their further meta- 
morphoses give rise to homologous products, but furnish 
neoplasms which in a greater or less degree are alien to 
the composition of the body. Every one of their ele- 
ments will withdraw matters from the body which might 
be used for other purposes, and as it has at the very out- 
set destroyed normal parts and even its first develop- 
ment presupposes the destruction of its parent structures 
it both plays a destructive part at the commencement of 
its career, and a depredatory one throughout its course. 





py 5h co ee ae A ie. pe. wr 


APRIL 27, 1858. 
FORM AND NATURE OF PATHOLOGICAL NEW-FORMATIONS. 


Nomenclature and classification of pathological new-formations—Consistence as a 
principle of division—Comparison with individual parts of the body—Histolo- 
gical division—Apparent heterology of tubercle, colloid, etc. 

Difference of form and nature: Colloid, Epithelioma, Papillary tumour, Tubercle. 

Papillary tumours: simple (condylomata, papillomata) and specific (villous cancer 
and cauliflower-tumour). . 

Tubercle: infiltration and granulation—Inflammatory origin of tubercle—Its origin 
from connective tissue—Miliary granules, and solitary masses—The cheesy 
metamorphosis. : 

Colloid: myxoma—Collonema—Mucous or gelatinous cancer. 

- Physiological types of heterologous new-formations: lymphoid nature of tubercle, 
hematoid of pus, epithelioid of cancer, cancroid, pearly and dermoid tumours, 
and connective-tissue-like of sarcoma—Infectiousness according to the amount 
of juice. 

Comparison between pathological new-formations in animals and vegetables—Con- 
clusion. 


Ir, gentlemen, we prosecute the train of thought which 
we have pursued in the last lectures, it seems to me that 
the question which you will perhaps next ask me, is, at 
what point the differentiation of new-formations really 
begins. You will remember that, according to our views 
the great majority of new-formations have their origin in 
connective tissue or parts equivalent to connective tissue, 
and that the first rudiments of all new-formations are 
nearly of the same nature, and that in particular the 


division of the nuclei, their multiplication, and the final 


507 
a 


508 LECTURE XxX. 


division of the cells show themselves in nearly all new- 
formations, in the benignant as well as in the malignant, 
in the hyperplastic as well as in the heteroplastic ones, 
in the self-same manner. Unquestionably, however, this 
similarity of nature is transitory ; it is not long before 
some, one characteristic feature displays itself in each in- 
dividual structure, whereby we are enabled distinctly to 
recognize its nature. 

With regard to this question of the criteria of new- 
formations, no agreement in opinion has indeed even at 
the present moment been come to, and here too there- 
fore it is incumbent upon me ‘now to show how I have 
arrived at my views, which in many respects so widely 
differ from those generally held, and for what reasons I 
have deemed myself obliged to quit the beaten track. 

The names which have been bestowed upon individual 
new-formations, have, as you know, often been. based 
pretty much upon accidental peculiarities, and not so very 
_unfrequently selected in quite an arbitrary manner. The | 
attempts to establish a regular nomenclature, which were 
formerly made, were really only based upon the consis- 
tence of tumours, reasons for classification having been 
derived from the circumstance that the substance of new- 
formations was found to be sometimes hard, at others 
soft, fluid, pultaceous, gelatinous, etc., and thus meliceris, 
atheromata, steatomata, scirrhi, etc., were separated from 
one another. It is self-evident that the ideas which are 
now attached to several of these things must be done 
away with, if it be wished to understand the original 
meaning of these designations. When the presence of 
an atheromatous process is now-a-days spoken of, some- 
thing is meant thereby of which the old observers were 
far from having any idea. When the tumour anatomists 
of the present day labour hard to revive the name stea-_ 
toma and would have it designate a firm fatty tumour, 


NOMENCLATURE OF NEW-FORMATIONS. 509 


you must remember that the manufacture of stearine was 
not known at the time when the term steatoma first came 
into use, and that the old observers never entertained the 
notion, which the tumour teachers of the present day 
cannot get out of their heads—that a steatoma* was a 
stearine- or indeed a fatty, tumour at all. 

The improved nomenclature which was introduced at 
the commencement of this century, was based more upon 
comparisons which were instituted between the new-for- 
mations and individual parts or tissues of the body. The 
term ‘medullary fungus” (Markschwamm) originally 
arose out of the idea that medullary cancers originated 
in the nerves and resembled nervous matter in their com- 
position. These comparisons have, however, until re- 
cently been always very arbitrary, because they were 
founded upon more or less rough resemblances in exter- 
nal appearance, without a due appreciation of the more 
delicate peculiarities of structure, and particularly of the 
_ really histological composition. 

Recently attempts have been made, and here and there 
even with great affectation, to make use of normal struc- 
tures as aids in terminology. Many attach a certain de- 
gree of importance to this, and consider it more scientific 
to say epithelioma, where others say cancroid or epithe- 
lial cancer. Thus in France great stress has, it is well 
known, been laid upon calling sarcomata fibro-plastic tu- 
mours, because Schwann and his followers looked upon 
caudate corpuscles as directly producing the fibres of con- 
nective tissue—which, in my opinion (p. 70), is an error. 
But in spite of these errors we must consider the histo- 
logical point of view as the true one, only it is not, I 
think, advisable, in accordance with this principle, at 
once to proceed to create new names for everything, and 


. ™ The ancients called any firm tumour (e. g., an enchondroma) a steatoma.— 
From a MS. Note by the Author. 


510 LECTURE XX. 


by means of these new names to render things which 
have long been known strange to the minds of people in 
general. Even new-formations which very evidently fol- 
low the type of some definite normal tissue, still for the 
most part possess peculiarities, whereby they may be 
more or less distinguished from this tissue, so that in the 
majority of cases, at least, it is by no means necessary to 
see the whole of the new-formation in order to know 
that this is not the normal, regular development of the 
tissue, but that on the contrary there is something in it, 
although it does not lose the type, which deviates from 
the ordinary course of homologous development. Be- 
sides there still remain even at the present time a certain 
number of new-formations, the external appearance or 
clinical character of which has, in part from the want of 
known physiological types, been retained as the basis for 
their names. 

We still continue to speak of tubercle, and the name 
which Fuchs has invented as a substitute, the only new 
one, as far as I know, which it has been attempted to 
introduce in its stead, Phyma, is so very indefinite, so 
readily applicable to every ‘‘ growth,” that it has met 
with no great favour. Several other names have been 
recently used to a continually increasing extent, which 
are also nothing more than stop-gags, as for example that 
of Colloid. This name was invented at the commence- 
ment of the present century by Laennec to designate a 
form of tumour which he described as analogous in con- 
sistence to half-set glue; in its well-developed form it 
constitutes a half-trembling gelly, colourless or of slightly 
yellowish hue, which on the whole conveys the impres- 
sion of a nearly complete absence of all structure. Whilst 
people formerly declared themselves perfectly content, 
when tumours of this kind were designated jelly-like, or 
gelatinous, to many of the more recent observers it has 





TUBERCLE—COLLOID. 511 


appeared a proof of superior penetration to say, instead 
of gelatinous tumour or gelatinous mass, colloid tumour 
or colloid mass. But you must not think that those, who 
have these denominations the most constantly in their 
mouths, intend to express anything else by them, than 
what most others call simply a jelly-like tumour, or only 
jelly. It is just the same with it, as, in the time of 
Homer, with the herb M4v, which was so called in the 
language of the gods, but by another name by men.* It 
is, however, very advisable, that these really unmeaning 
and only high-sounding expressions should not be unne- 
cessarily diffused, and that the habit should be acquired 
of conveying a precise meaning by every expression, and 
that therefore from the moment one really aspires to 
make histological divisions, one should no longer employ, 
when speaking of every jelly-like tumour, the term col- 
loid which has no histological value whatever, but merely 
designates an external appearance which tissues of the 
most different nature may under certain circumstances 
present. Laennec himself inaugurated the somewhat 
pernicious practice, by speaking of a colloid transforma- 
tion of fibrinous exudations of the pleura. 

The chief difficulty, which here presents itself, consists 
in this, that people do not know how to discover any 
difference between the mere form and the true nature. 
The form ought only to be admitted as a decisive crite- 
rion for the diagnosis of new-formations, when it is con- 
joined with a real difference in the tissue, and does not 
result from accidental peculiarities of situation or posi- 
tion. If, for example, you wish to make use of the name 
colloid, you can do so in two ways. You can either 
employ it to designate nothing more than a kind of 
appearance, and then you will certainly be able to find 


f Odyss. X. 305. Note of the Stenograph. 


512 LECTURE XxX. 


different tumours which you can distinguish from other 
tumours of the same genus by means of the addition 
‘‘colloid.”” You may therefore say: colloid cancer, col- 
loid sarcoma, colloid fibroma [fibrous (connective-tissue) 
tumour]. Here colloid means nothing more than jelly- 
like. Or you must have a distinct notion of the nature, 
of the chemical or physical peculiarities of the colloid 
substance, or of the morphological nature of the colloid 
tissue, and then it will be impossible for you to class 
together two, chemically and morphologically, entirely 
different products, such as the colloid of the thyroid body 
and colloid cancer. 

In just the same manner we see that a great number 
of tumours, when they are seated on the surface, give 
rise to excretions, which, according to the nature of the 
surface, appear in the form of villi, papilla or warts. All 
these tumours may be comprised under one name and 
called papillomata, but the tumours which have this form 
often differ toto coelo from one another. Whilst in the 
one case we have a true hyperplastic development, we 
find in another, at the base of these villi where they rest 
upon the skin or mucous membrane, some specific form — 
of tumour. In many cases even the villi themselves are 
filled with a substance analogous to that of the tumour. 
This is a very important difference. If, for example, you 
examine a broad condyloma, the mucous tubercle or 
plaque muqueuse of Ricord, you will find, under the 
epidermis which still remains smooth, the papilla enlarg- 
ing and ultimately growing out into branched figures so 
as to represent regular trees. Cancer, however, may give 
rise to excrescences of the same shape as these condy- 
lomata. This we see comparatively less frequently occur 
on the skin than on the different mucous surfaces. In 
these cases it may happen that real cancer: is seated in 
the villi. Nor is: this in itself indeed at all surprising 














PAPILLOMATA, (CONDYLOMATOUS AND CANCEROUS). 513 


The papille consists of connective tissue like the skin, or 
the mucous membrane, upon which they are seated ; 
within the papille therefore a cancerous mass may 
develop itself out of the connective tissue, as out of the 
connective tissue of the skin or mucous membrane. 
Moreover, it cannot be denied that this peculiarity of 
superficial formation very frequently explains certain 
peculiarities in the course of the disease, whereby a papil- 
lary tumour is strikingly distinguished from the same 
kind of tumour when not papillary. Any one may have 
a cancer of the bladder—if it be merely seated in the pa- 
rietes—for a very long time, without any other changes 
being necessarily displayed in the nature of the secretion, 
which must be evacuated with the urine, than those 
exhibited in a simple catarrh. As soon, on the contrary, 
as a formation of villi takes place upon the surface, nothing 
is more common than for hematuria to arise as a com- 
plication, from the simple reason, that every villus upon 
the walls of the urinary bladder is not clothed with a 
firm layer of epidermis, but lies almost bare under a 
loose epithelial covering. Into the interior of the villi 
ascend large vascular loops which reach quite up to the 
surface, and therefore very considerable mechanical irri- 
tation supplies a condition for the production of hy- 
pereemia and the rupture of the villi. A spasmodic 
contraction of the bladder drives the blood up into the 
apices of the villi, in consequence of the shortening of the 
surface on which they are seated, and when to this is 
added the mechanical friction of the surfaces, nothing is 
more likely to ensue than a sometimes more, sometimes 
less considerable effusion of blood. But in order that 
such hemorrhage should take place it is altogether unne- 
cessary that the papillary tumour should be cancerous. I 
have seen cases in which, for years, uncontrollable bleed- 


ings recurred from time to time, through which at last the 
33 


514 LECTURE XX. 


patients died aneemic, and yet no trace of any cancerous 
infiltration of the base of the growth or of the villi ex- 
isted, but the tumour was quite a simple papillary one, a 
benignant formation, which on the surface of the skin 
could easily have been removed by the knife or ligature, 
but which, owing to its concealed position, was in these 
cases attended with a series of phenomena, which during 
life it seemed impossible to refer to anything else than a 
really malignant new formation. 

Just the same is the case with the much-discussed 
cauliflower-tumours, as they are seen on the surface of the 
genital organs, both in man and woman. In men, these 
papillary tumours, which proceed from the prepuce and 
surround the corona glandis, are for the most part covered 
by a very thick layer of epidermis, so that, when they 
ulcerate, they yield but a very trifling amount of secre- 
tion. In women, on the contrary, the tumour being 
seated on the neck of the uterus—a very vascular part, 
provided with a thin stratum of epithelium, and natu- 
rally beset with a thick layer of numerous and large 
papille—for the most part very early occasions abun- 
dant transudations and occasionally hemorrhagical exu- 
dations of a fluid, like water in which raw meat has been 
soaked, or really red and bloody. In these cases there 
frequently exists doubts as to the nature of the disease. 
I myself was present when a very renowned surgeon 
came to Dieffenbach’s operating room, just as that ope- 
rator had amputated a penis on account of a ‘‘ carcinoma ” 
-—and when the stranger afterwards declared it to have 
been a simple condyloma. On the other hand I have 
examined cases, in which growths of this sort had been 
doctored about for years as if they had been syphilitic 
condylomata, because the external appearance is so ex- 
tremely analogous, and it is so extremely difficult to dis- 
cover a criterion by which it can be accurately determined 
































enna 








CAULIFLOWER TUMOURS. 515 


whether the formation only imvolves the surface, or 
whether it is complicated with disease of the subjacent 
tissue. There are certainly at the present time very 
many anatomists and surgeons who entertain the notion 
that cells may grow on the surface exactly similar to 
those which are usually only found in the interior of dis- 
eased organs—that, for example, a villous tumour must 
be termed cancerous, if it is covered over with cancer- 
cells as with an epithelium, without any development of 
cancerous matter having shown itself in the interior 
of the villi. In fact, villi, which are very delicate and 
scarcely contain enough connective-tissue to envelop the 
vessels that run up in them, are sometimes met with, 
enclosed in a thick layer of cells which, from the irregu- 
larity of their form, the size of their nuclei, and their own 
large dimensions, present rather the character of cancer 
than that of epithelium. But I must confess that I have 
not as yet been able to convince myself that cancer-cells 
are able to arise upon the free surfaces of membranes, 
and that they can be produced simply from epithelium ; 
on the contrary, I believe from all that I have seen, that 
a very strict line of demarcation must be drawn between 
the cases, where masses of cells, however abundant and 
curiously shaped they may be, are found seated upon a’ 
basis-tissue in itself unaltered, and those, where the cells 
have been formed in the parenchyma of the parts them- 
selves. 

The pathological importance of a papillary tumour is, 
at least as far as I know, determined by the condition 
of its basis-substance, or by that of the parenchyma of the 
villi themselves ; and a formation can only be pronounced 
to be cancroid or carcinoma when, in addition to the 
growth of the surface, the peculiar degenerations which 
characterize these two kinds of tumours, take place also 
in the deeper layers or in the villi themselves. I think, 


516 LECTURE XX. 


therefore, that all these external differences of form can 
only serve to distinguish different species of the same 
genus of tumours, but by no means different tumours, 
from one another. There are connective-tissue [fibrous] 
tumours of the surface, which manifest themselves in the 
form of simple tubera (Knoten *), others which show 
themselves in the form of warts and papillary tumours. 
In just the same manner, there are cancerous formations 


Fig. 1389. 


Za = 
SSS 
SSS = 


N 
% 
S 
& 


LE UY Ye, 


y SiS 3) 
SSSAN\ ISS\ 


WSS 





Fig. 139. Vertical section through a commencing cauliflower growth (cancroid) 
of the neck of the uterus. On the still unchanged surface the tolerably large 
papille of the os uteri are seen invested by a homogeneous, stratified layer of epi- 
thelium. The disease begins first on the other side of the mucous membrane in the 
real parenchyma, of the cervix, where large, roundish or irregular, scattered groups 
of cells (contained in alveoli) are disseminated throughout the tissue. 150 diame- 
ters. 


* The term Knoten (Eng. knot, Lat. ¢uber) having reference rather to the form 
than to the size of the tumour, is used in this work as a designation for all sorts of 
tuberiform tumors, even the largest.—Zrans. 








— ee 














PAPILLARY TUMORS. 517 


and cancroid formations which may assume “this form, 
and others again, which do not do so. 

_With reference to the relation of form and nature, there 
is a question of really cardinal importance, concerning 
which, in the interest of mankind, a certain degree of 
unanimity ought soon to be arrived at, namely, what is 
properly to be understood by the term tubercle. The 
same difficulties which I have just described to you, are 
again encountered in the case of tubercle in a still higher 
degree. The old writers introduced the name tubercle 
merely to express an external form. Everything was 
called a tubercle which manifested itself in the shape of 
a small knot. It is, as you are no doubt aware, by no 
means so very long since this term was employed in the 
most loose manner. Carcinomatous and scirrhous tuber- 
cles were talked about, scrofulous and syphilitic tubercles 
were distinguished from one another, and these terms are 
still preserved in France. Cancer too, you know, in old 
times was not by any means exclusively employed to 
designate a real tumour, but noma (cancer aquaticus) was 
considered to have as much right to the appellation as a 
chancre (cancer syphiliticus). 

Now in the course of the present century endeavours 
have been made gradually to exchange these somewhat 
superficial views for more accurate conceptions, and here 
also it is to Laennec especially that credit is due for hav- 
ing sought for: precise denominations. Still he himself 
in his turn has been the cause of this matter’s having 
fallen into a state of nearly irremediable confusion. For, 
as you no doubt recollect, he asserted that tubercle pre- 
sented itself in the lungs under two different aspects, the 
so-called tubercular infiltration, and tubercular granula- 
tion. Now, inasmuch as infiltration signifies something 
completely at variance with the old notion of tubercle, 
since it does not at all imply the presence of small knots 


518 LECTURE XX. 


(Knétchen), but expresses an equable pervasion of the 
whole parenchyma, a track was hereby opened, in follow- 
ing which the old idea of tubercle has more and more 
been departed from. Assoon as the infiltration of tuber- 
cle had once been created and the form of the neoplasm: 
had thereby been abandoned, the infiltration was gene- 
rally, as being more extensive and therefore more instruc- 
tive, taken as the basis of subsequent descriptions, and 
attempts were made to find out in what respects it really 
agreed with the other, previously known forms of tuber- 
cle. It was in this way, that the cheesy stage of tubercle 
came to be gradually adopted as the common generic 
characteristic of all tuberculous products, not merely as 
the principal aid in diagnosis, but as the starting-point 
for the interpretation of the process in general. It was 
in this way, in particular, that the idea came to be enter- 
tained, that tubercles could arise simply by any exuda- 
tion’s losing its water constituents, growing thick, turbid, 
Opaque, cheesy, and remaining in this condition. 

The term, tubercle-corpuscles (corpuscules tubercu- 
leux), which is, you know, still in very frequent use, has 
_ reference to just this cheesy stage, and the accurate de- 
scription which Lebert has given of them amounts to this 
—that they are formations which correspond with none 
of the known organic forms, and are neither cells, nor 
nuclei, nor anything else of an analogous nature, but 
appear in the form of little, roundish, solid corpuscles, 
which frequently have particles of fat scattered through 
them (Fig. 64). But if the development of these corpus- 
cles be investigated, it is easy to convince oneself that, 
wherever they occur, they arise out of previous organic 
morphological elements, and that they are not by any 
means the first bungling products, unfortunate essays of 
organization, but that they were once well-grown elements, 
which by an unhappy chance were early checked in their 


TUBERCLES. 519 | 


development and early succumbed to a process of shri- 
velling. You may with certainty assume that, where 
you meet with a largish corpuscle of this description, a 
cell had previously existed, and where you find a small 
one, there once had been a nucleus, enclosed perhaps 
within a cell. 

Upon examining the point which has been the leading 
one in the doctrine of tuberculosis recently advanced, 
namely tubercular infiltration of the lungs, we readily 
arrive at the result which Reinhardt has set down as the 
final one, namely, that tuberculosis is nothing more than 
one of the forms presented by inflammatory products 
when undergoing transformation, and especially that all 
tuberculous matter is really inspissated pus. In fact, 
what has been termed tubercular infiltration, can with 
few exceptions be traced to an originally inflammatory, 
purulent or catarrhal mass which has gradually, in con- 
sequence of incomplete reabsorption, fallen into the shri- 
velled and shrunken state in which it afterwards remains. 
But Reinhardt was deceived when he thought he was ex- 
amining tubercle. He was led astray by the false direc- 
tion which had been given to the whole doctrine of tu- 
berculosis from the time of Laennec until his own, espe- 
cially through the fault of the Vienna school. If he had 
confined himself in his investigations to the form of old 
assigned to tubercle, and knot (granule), if he had ex- 
amined the constitution of the knot in its different stages 
and had afterwards compared the different organs in 
which knotted (granular) tubercle occurs, he would un- 
questionably have arrived at a different result. 

It may, at least according to what I consider to be the 
correct view of the matter, certainly be said, that the 
greatest part of whatever in the course of tuberculosis 
does not appear in the form of granules, is an inspissated 
inflammatory product, and has at any rate no direct rela- 


520 LECTURE XX. 


tion to tubercle. But by the side of these inflammatory 
products, or also independently of them, we find a pecu- 
liar structure [the knot, granule] which, if they are to 
be regarded as real tubercle, would no longer be included 
in the ordinary classification ; and it is certainly an ex- 
tremely characteristic circumstance that in France, where 
the terminology of Lebert has become the prevailing one, 
and the corpuscules tuberculeux are wont to be regarded 
as the necessary accompaniments of tuberculosis—bodies, 
concerning the tuberculous nature of which there can be 
no doubt, have quite recently been set down as some- 
thing altogether peculiar and which had hitherto re- 
mained undescribed. For one of the best, nay perhaps 
the best, micrographer France possesses, Robin, has, in 
his examinations of cases of tubercular meningitis, deemed 
it impossible to regard the little granules in the arach- 
noid* [pia mater] which every body looks upon as tu- 
bercles, as being really tubercles, because the dogma 
now prevails in France that tubercle consists of solid 
non-cellular corpuscles, and in the tubercles of the cere- 
bral membrane cells in a state of perfect preservation are 
met with. To such curious aberrations does this track 
lead that one ends by being unable to find a name for 
real tubercle, because so many accidental objects have 
been confounded with it, that what was sought for, or 
even what had been found and was already grasped, has, 


* The so-called visceral (cerebral) layer of the arachnoid is: only the superficial 
layer of the pia mater which is spread evenly over, and does not dip in between, 
the convolutions, and being (as the name, arachnoid, implies), of a reticulated tex- 
tare contains spaces (subarachnoid spaces). The so-called parietal layer of the 
arachnoid is only the inner superficial layer of the dura mater with the epithelium 
lining it. The Author employs the term arachnoid in general only for the purpose 
of making himself more intelligible to others, but as this superficial layer of the 
dura mater does not possess a reticulated structure and is everywhere inseparably 
connected with the rest of the membrane, and as epithelial coverings are not wont 
to be designated by special names, he of course always uses the term of the pia 
mater. Such expressions, therefore, as the “sac” or “cavity of the arachnoid ” 
are incorrect.—Based upon MS. Notes by the Author. 


TUBERULES. | 521 


in consequence of the attention of observers being 
diverted by these objects, been allowed to slip out of 
one’s hand again. I am of opinion that a tubercle is a 
granule, or a knot, and that this knot constitutes a new- 
formation, and indeed one, which from the time of its° 
earliest development is necessarily of a cellular nature, 
and generally, just like all other new-formations, has its 
origin in connective tissue, and which, when it has 
reached a certain degree of development, constitutes a 
minute knot within this tissue, that, when it is at the sur- 
face, projects in the form of a little protuberance, and 
consists throughout its whole mass of small uni- or multi- 
nuclear cells. What especially characterizes this forma- 
tion is the circumstance, that it is extremely rich in nu- 
clei, so that when it is examined as it lies imbedded in 


Fig. 140. 





the tissue which invests it, at the first glance there seems 
to be scarcely anything else than nuclei. But upon iso- 
lating the constituents of the mass, either very small cells 
provided with one nucleus are obtained—and these are 
often so small that the membrane closely invests the nu- 
cleus—or larger cells with a manifold division of the nu- 


Fig. 140. Development of tubercle from connective tissue in the pleura. The 
whole succession of transitions is seen from the simple connective-tissue corpuscles, 
the division of the nuclei and cells up to the production of the tubercle-granule, the 
cells of which in the middle are disintegrating into fatty granular débris. 800 
diameters. 


599 ' LECTURE XX. 


clei, so that from twelve to twenty-four or thirty are 
contained in one cell, in which case, however, the nuclei 
are always small and have a homogeneous and somewhat 
shining appearance. 

This structure, which in its development is compara- . 
tively most nearly related to pus, inasmuch as it has the 
smallest nuclei and relatively the smallest cells, is distin- 
guished from all the more highly organized forms of can- 
cer, cancroid and sarcoma, by the circumstance, that 
these contain large, voluminous, nay often gigantic cor- 
puscles with highly developed nuclei and nucleoli. Tu- 
bercle, on the contrary, is always a pitiful production, a 
new-formation from its very outset miserable. From its 
very commencement it is, like other new-formations, not 
unfrequently pervaded by vessels, but when it enlarges, 
its many little cells throng so closely together, that the 
vessels gradually become completely impervious and only 
the larger ones, which merely traverse the tubercle, re- 
main intact. Generally fatty degeneration sets in very 
early in the centre of the knot (granule), where the oldest 
cells lie (Fig. 140), but usually does not become com- 
plete. Then every trace of fluid disappears, the corpus- 
cles begin to shrivel, the centre becomes yellow and 
opaque, and a yellowish spot is seen in the middle of the 
grey translucent granule. This is the commencement of 
the cheesy metamorphosis which subsequently characterizes 
the tubercle. This change advances from cell to cell far- 
ther and farther outwards, and it not unfrequently hap- - 
pens that the whole granule is gradually involved in it. 

Now, the reason why I think that the name of tuber- 
cle must be specially retained for this formation as being 
extremely characteristic of it, is this—that the tubercle- 
granule never attains any considerable size, and that a 
tuber never arises out of it. Those which are wont to be 
termed large tubercles, and attain the size of a walnut, or 


SOLITARY TUBERCLES OF THE BRAIN. 523 


a Borsdorf apple,* as for example in the brain—those 
are not simple tubercles. You will generally find the 
tubercles in the brain described as being solitary, but 
they are not simple bodies; every such mass (tuber) 
which is as large as an apple, or even not larger than a 
walnut, contains many thousands of tubercles ; it is quite 
a nest of them which enlarges, not by the growth of the 
original focus (granule), but rather by the continual for- 
mation and adjunction of new foci (granules) at its cir- 
cumference. If we examine one of these perfectly yel- 
lowish white, dry, cheesy tubera, we find immediately 
surrounding it a soft, vascular layer which marks it off 
from the adjoining cerebral substance—a closely invest 
ing areola of connective tissue and vessels. In this layer 
lie the small, young granules, now in greater, now in 
less, number. They establish themselves externally [to 
the previously existing ones] and the large tuber grows 
by the continual apposition of new granules (tubercles), 
of which every one singly becomes cheesy ; the whole 
mass, therefore, cannot in its entirety be regarded as a 
simple tubercle. The tubercles themselves remain really 
minute, or as we are wont to say, mary. Even when 
on the pleura, by the side of quite small granules, large 
yellow plates, looking as if they were deposited upon the 
surface, are met with, these too are not simple tubercles, 
but masses composed of a large aggregate of originally 
separate granules. | 
Here, you see, form and nature are in reality insepara- 
bly connected. The form is produced by the growth of 
the tubercle from single cells of connective tissue, by the 
degenerative proliferation of single groups of connective- 
tissue corpuscles. Thus, without more ado, it appears 


_ * Borsdolf apples are very constant in their size, and measure from an inch and a 


half to an inch and three quarters (1}”—1#") in diameter.—From a MS. Note by 
the Author. 


324 | ~ ECTURE XX; 


at once in the shape of a granule. As soon as it has 
once attained a certain size, as soon as the generation of 
new corpuscles which develop themselves out of the old 
histological elements by a continual succession of divi- 
sions, at last lie so close to one another as to cause a 
mutual arrest of development, gradually to induce the 
disappearance of the vessels of the tubercle, and thereby 
to cut off their own supplies, then they begin to break up, 
they die away and nothing remains behind but débris— 
shrunken, disintegrated, cheesy material. 

The cheesy transformation is the regular termination 
of tubercle, but, on the one hand, it is not the necessary 
‘one, inasmuch as there are rare cases, in which tubercles, 
in consequence of their undergoing a complete fatty me- 
tamorphosis, become capable of reabsorption ; and, on 
the other hand, the same cheesy metamorphosis befalls 
other kinds of cellular new-formations ; for pus may be- 
come cheesy, and likewise cancer and sarcoma. This 
metamorphosis, therefore, being common to more than 
one formation, cannot well be set down as a criterion for 
the diagnosis of any particular structure, such as tuber- 
cle ; on the contrary, there are certain stages in its re- 
trograde metamorphosis, where one cannot help confess- 
ing that it is not always possible to come to a decision. 
If a lung be laid before you with cheesy masses scattered 
through it, and you are asked if that be tubercle or no, 
you will frequently be unable to say with certainty what 
the individual masses originally were. There are periods 
in the course of development, when that which is inflam- 
matory and that which is tuberculous can with precision 
be distinguished from one another; but, at last, there 
comes a time, when both products become confounded, 
and when, if one does not know how the whole arose, no 
Opinion can any longer be formed as to what its nature 
is. In the midst of cancerous masses also cheesy spots 


* 


CHEESY METAMORPHOSIS (TUBERCLE, CANCER). 525 


occur which look exactly like tubercles. I have demon- 
strated that it is by the gradual transformation of the 
elements of cancer that this cheesy matter is produced. 
But if we did not positively know from the history of 
their development that cancer-cells disintegrate step by 
step, and that no tubercles form in the middle of cancer, 
we should in many cases be altogether unable to arrive 
at any decision from merely examining the specimen. 

If those difficulties be surmounted which lie in the 
external appearance of the formation, and lead the ob- 
server astray not only when he considers its grosser 
features, but also when he investigates its more intimate 
composition, there remains nothing else to assist us in 
coming to a right conclusion than the investigation of the 
type of development displayed by the individual new-for- 
mations during the stages of their actual development, 
not during those of their retrograde metamorphosis. 
The nature of tubercle cannot be studied after the period 
when it becomes cheesy, for from that time its history is 
identical with the history of pus which is becoming 
cheesy ; an earlier period must be chosen when it is 
really engaged in proliferation. So in the case of other 
formations, that period must be studied which is com- 
prised between their origin and their culminating point, 
and we must see with what normal physiological types 
they agree. Then it is, I think, certainly possible for us 
to arrive at a just conclusion with the aid of the simple 
principles of histological classification, which I have 
already propounded to you (p. 91). Heterologous tissues 
also have physiological types.* 

A colloid growth, if we really take it to mean what 
Laennec did—a gelatinous organized new-formation— 
must necessarily correspond to some type to be met with 
in the body when in its normal condition. Thus there 
are a series of tumours, that have been included in the 


596 LECTURE XX. 


colloid class, which have altogether the structure of the 
umbilical cord, and which, like this part, essentially con- 
tain mucus in their intercellular substance. Now since I 
had named the tissue of the umbilical cord and analogous 
parts, mucous tissue, it is a very simple step for me to 
call these tumours Mucous tumours (Schleimgeschwiilste), 
Myxomata. When we demonstrate the occurrence of 
tumours exhibiting the histological type of the umbilical 
cord in the midst of the adult body, the striking charac- 
ter of the phenomenon is in no wise lessened, but we 
have found for them a type among the normal tissues of 
the body. Another form of colloid, or as Johannes Miil- 
ler has called it, Collonema, turns out to be merely oede- 
matous connective tissue. We find nothing more than a 
very soft tissue, soaked in an albuminous fluid. Such a 
tumour cannot be separated from connective-tissue 
[fibrous] tumours generally, whether they be denomi-- 
nated gelatinous, oedematous, or sclerematous* connec- 
tive-tissue tumours, and I think there is no occasion to 
estrange it from the mind by bestowing upon it the name 
of collonema. So, again, we find certain forms of can- 
cer, in which the stroma, instead of being composed 
simply of connective tissue, consists of the same mucous 
tissue which we meet with in a simple mucous tumour. 
These we may simply name Mucous Cancer (Gelatinous 
or Colloid Cancer). We then know exactly what we 
have before us. We know it is a cancer, but that its 
stroma differs in its containing mucus and in its gelati- 
nous nature from the ordinary stroma of cancers. 

To revert once more to the consideration of tubercle— 
it would certainly be something completely abnormal if 
it were composed of corpuscles tuberculeux ; but if you 
compare the cells which are, as at least I must assume to 


* Sclerema=cedema durum, 





LYMPHOID NATURE OF TUBERCLE. 527 


be the case, the real constituents of the granule, with 
normal tissues of the body, you will remark the most com- 
plete correspondence between them and the corpuscles 
of the lymphatic glands, and this is a correspondence 
which is neither accidental nor unimportant, for was it 
not known even of old, that lymphatic glands have an 
especial tendency to undergo the cheesy degeneration ? 
Even the old writers have stated that a lymphatic consti- 
tution disposes to processes of this kind. 

With regard to pus, I need only remind you that we 
have been occupied during several lectures in discussing 
the question of, the possibility of, diagnosing between 
pyzemia and leucocytosis, and that we have recognized 
in the colourless corpuscles of the blood bodies so per- 
fectly analogous to pus-corpuscles, that some have thought 
they saw pus when they had colourless blood-corpuscles 
before them, whilst Addison and Zimmermann, on the 


, contrary, imagined they had found colourless blood-cor- | 


puscles when they really were looking upon pus. Both 
have a like type of formation. It may therefore be said 
that pus has a hematoid form, nay, the old doctrine may 
be revived afresh, namely, that pus is the blood of patho- 
logy. But if one would seek a distinction, if one would 
be able to say in individual cases what is pus and what 
blood-corpuscles, there is no other criterion than to deter- 
mine whether the cell arose at a spot where a colourless 
blood-corpuscle might be expected to arise, or at one 
where it ought not be produced. 

So, moreover, we find amongst pathological new-for- 
mation a large category, the natural type of which is 
epithelium—Epitheliomata, if you will. But the term 
epithelioma, which has recently been introduced by Han- 
nover, is completely inadmissible in the case of the par- 
ticular kind of tumour which it was intended to designate, 
because the epithelioma is by no means the only tumour 
whose elements bear the character of epithelial cells. 


598 LECTURE XX. 


Epithelioma cannot be distinguished from other tumours 
by its elements’ having the character of epithelium whilst 
those of the others have it not. The tumour that 
[Johannes] Miiller called Cholesteatoma, Cruveilhier, 
tumeur perlée—which I have translated Perlgeschwulst 
[pearly tumour]—this tumour has exactly the same epi- 


Pie. 141, 





Fig. 141. Solid mass of cancroid from a tumour of the underlip. Closely packed 
layers of cells at the circumference, presenting all the characters of the rete Malpi- 
ghii: in one of the processes, globules glistening like fat; in the middle of the body 


of the growth, a horny, epidermoidal, hair-like structure, with onion-like globules 
(pearls, globes épidermiques). 300 diameters. 








EPITHELIOID NEW-FORMATIONS. 529 


thelial structure as that which Hannover has called 
epithelioma, nay, ordinary epithelioma very commonly 
engenders in itself little pearly globules in an often 
astonishingly great number. Yet both exhibit very 
essential points of difference. Never as yet have any 
pearly tumours been seen which, after existing in one 
place, recurred in remote places, and behaved like malig- 
nant tumours ; never did anything else occur than a slight 
extension—and that at an extremely slow rate—to the 
immediate neighborhood of the tumour. In the case of 
epitheliomata on the other hand, or as they are otherwise 
called, epithelial cancer or cancroid, we see a very 
marked malignity, for not only are they liable to recur at 
their original site, but they also reproduce themselves in 
distant parts. In many cases nearly all the organs of the 
body are metastatically filled with masses of cancroid. 
Again, if you attempt to dis- 


‘tinguish cancroid growths from Fig. 142. 


real cancer by the epithelial 
structure of their elements, you 
will herein too give yourselves 
trouble in vain. Cancer proper 
has also elements of an epithelial 
character, and you need only 
turn to those parts of the body,« 
where the epithelial cells are 
irregularly developed, as for ex- 
ample in the urinary passages 
(Fig. 15), and you will meet with 
the same curious bodies, provided 
with large nuclei and nucleoli, which are described as 
the specific, polymorphous cells of cancer. Cancer, can- 
croid or epithelioma, pearly tumours or cholesteatoma, nay 





Fig. 142. Various, polymorphous ecancer-cells, some of them in a state of fatty 
degeneration, two with multiplication of nuclei. 300 diameters. 
84 


530 LECTURE XX. 


perhaps the dermoid growths which produce hairs, teeth, 
and sebaceous glands, and so frequently occur in the ovary 
—all these are formations in which there is a pathological 
production of epithelial cells, but they constitute a gradu- 
ated series of different kinds, which extend from those 
which are entirely local, and, in the usual meaning of the 
word, perfectly benignant, to the extremest malignity. 
The mere form of the cells which compose a structure, is 
of no decisive value. Cancer is not malignant because 
it contains heterologous cells, nor cancroid benignant 
because its cells are homologous—they are both malig- 
nant, and their malignity only differs in degree. 

The forms which yield dry, juiceless masses, are rela- 
tively benignant. Those which produce succulent tissues 
have always more or less a malignant character (p. 251). 
The pearly tumour, for example, yields perfectly dry epi- 
thelial masses, almost without a+race of moisture, and it 
only infects locally. Cancroid remains for a very long 


Fig. 148. 


\ 
Wy a) 


EN 
Bee 





Fig. 148. Section through a cancroid of the orbit. Large epidermic globules 
(pearls), laminated after the manner of an onion, in a closely packed mass of cells, 
which have partly the character of epidermis, partly that of rete Malpighii. 150 
diameters. 


SARCOMA. 


531 


time local, so that the nearest lymphatic glands often do 
not become affected until after the lapse of years, and then 
again the process is for a long time confined to the disease 
of the lymphatic glands, so that a general outbreak of the 
disease in all parts of the body does not take place until 
late, and only in rare instances. In cancer proper the 
local progress is often very rapid and' the disease early 
becomes general ; acure, even for a short, time is so rare, 
that in France the complete incurability of cancer properly 
so called has been asserted and maintained with success. 


Among the formations also which 
are analogous to the ordinary con- 
nective tissues, and are therefore 
apparently perfectly homologous and 
benignant, the succulent ones prove 
to be much more capable of commu- 
nicating infection than.the dry ones. 
A myxoma which has always a good 
deal of juice about it, is at all times 


a suspicious tumour, and, in propor- 


tion to the quantity of juice it con- 
tains, is its liability to recur. Car- 
tilaginous tumours (Enchondromata) 
which were formerly described as 
unquestionably benignant, sometimes 


occur in soft and rather gelatinous: 


forms, which may occasion just such 
internal metastases as cancer pro- 
perly so-called. Even connective- 
tissue * [fibrous] tumours become, 
under certain circumstances, rieher 
in cells and enlarge, whilst their 
interstitial connective tissue becomes 


Fig. 144. 





Fig. 144, Diagrammatic representation of the development of sarcoma, as it may 


very well be seen in sarcoma of the breast. 350 diameters, 


* Fibrous tissue is dense connective tissue. It is not a special tissue, but only a 


532 LECTURE XX. 


more succulent, nay in many cases disappears so com- 
pletely, that at last scarcely anything but cellular ele- 
ments remain. This is the kind of tumour which, 
according to my opinion, ought to be designated by the 
old name of Sarcoma. These sarcomata are frequently, 
indeed benignant, still they do not unfrequently recur, 
like epithelial cancer, at their original site, whilst under 
certain circumstances they appear secondary in the lym- 
phatic glands, and in many cases’ occur throughout the 
whole body metastatically to such an extent, that scarcely 
any organ is spared by them. 

In the case of all these formations, every one of which 
corresponds more or less completely to a normal tissue, 
investigations ought not to be conducted with a view to 
determine whether they have a physiological type, or 
whether they bear a specific stamp impressed upon them ; 
our final decision depends upon the answer to the ques- 
tion, whether they arise at a spot to which they belong, or | 
not, and whether they produce a fluid, which, when brought — 
into contact with the neighbouring parts, may there exercise — 
an unfavourable, contagious or wrritative influence. 

It is with these formations as with vegetable ones. 
The nerves and vessels have not the slightest direct influ- 
ence. They are only of importance so far as they deter- 
mine the greater or less abundance of supply ; they are 
altogether unable to impel to the development of tumours, 
to produce them or to modify them in a direct manner. 
A pathological tumour in man forms in exactly the same 
way that a swelling on a tree does, whether on the bark,. 
or on the surface of the trunk or a leaf, where any patho- 
logical irritation has occurred. The gall-nut which arises 


form of connective tissue. Periosteum, perichondrium, tendons &c. all of them con- 
sist of connective tissue, in which, however, the cells have in part become converted 
into elastic fibres and network. In Germany indeed connective (cellular) tissue has 
ever since the time of Treviranus (1835) been divided into formed and formless, the 
former including tendons, fascie, ligaments, &.—From a MS. Note by the Author. 


TUMOURS OF PLANTS. 533 


in consequence of the puncture of an insect, the tuberous 
swellings which mark the spots on a tree where a bough 
has been cut off, and the wall-like elevation which forms 
around the border of the wounded surface produced by 
cutting down a tree, and which ultimately covers in the 
surface—all of them depend upon a proliferation of cells 
just as abundant and often just as rapid as that which 
we perceive in a tumour of a proliferating part of the 
human body. The pathological irritation acts in both 
cases precisely in the same manner; the processes in 
plants conform entirely to the same type, and just as lit- 
tle as the tree produces on its bark or leaves cells of a 
kind, which it could not bring forth at other times, just 
as little does the animal body do this. 

But if you consider the history of a vegetable tumour, 
you will see there also that it is above all the diseased 
spots which become unusually rich in specific constitu- 
ents, and absorb and store up the peculiar substances 
which the tree produces, in more than average quantity. 
The vegetable cells which form on an oak-leaf round the 
puncture made by an insect contains much more tannic 
acid than any other part of the tree. The tumour-cells 
which form with such exuberance in a pine at the spot 
where an insect has buried itself in the young trunk, are 
stuffed completely full of resin. The peculiar formative 
energy which is developed at these spots, occasions also 
an unusually abundant accumulation of juicés. There 
is no need of any nerves or vessels to instigate the cells 
to an increased absorption of matter. It is by their own 
action—by means of the attraction which they exercise 
upon the neighboring fluids—that they draw in the most 
serviceable materials. The great importance, which a 
knowledge of botany possesses for the pathologist also, lies 
in this—that it enables him to discover in all these pro- 
cesses the existence of an inward correspondence in the 


534 LECTURE XX. 


whole series of vital phenomena, and to show how the 
lowest formations may serve to explain the history of the 
most perfect and complex parts. 


I have in the course of these lectures, gentlemen, deve- 
loped to you as completely as it was possible for me 
here to do, the principles by means of which alone it is, 
according to my experience, possible to come ‘to any cor-, 
rect decision in the case of pathological pfocesses. I 
heartily thank you for the lively interest which you have 
testified to me up to the last moment. I perfectly know 
how to appreciate the fact that men like you, whose time 
is taken up by such manifold labours, still retain a taste 
for discussions of this kind, and I only wish that many a 
useful view of recent date may have been rendered more 
intelligible to you by these lectures, and that the facts I 
have laid before you may furnish you with recollections 
which may prove of service in your practice. 


Abscesses, cold, inspissation of pus in, 
216; formation of, 496-497. 

Absorption, increased, of parts upon 
the application of stimuli, 155, 336, 
etc. 

Activity, the essential characteristic of 
life, 8324; see Vital activity. 

Addison, Mr., on the relation between 
pus-, and colourless blood-corpuscles, 
188, 527. 

Adipose Tissue. See Fat. 

Affinities, certain, between definite tis- 
sues (parts) and definite substances, 
154, 158; specific, of different exci- 
tants (stimuli), 332. 

Ague, melanemia in, 256-257. 

Alw vespertitionum, smooth muscle in, 
146, 147. 

Alveoli, of cancer, how produced,, 499. 

Amaurosis, from capillary embolia, 244. 

Amyloid (lardaceous, waxy) Degenera- 
tion, 409-427; appearance of organs 
affected, 410; occurs in most parts of 
body, 411; of minute arteries, 416- 
417; of liver (hepatic artery, hepatic 
cells), 417-418 ; its concomitants, 421 ; 
of digestive tract from mouth to anus 
minute arteries, villi), 422; of kidney, 
peptone afferent arteries), 422; of 
lymphatic glands (minute arteries, 
gland cells), 425-427; of spleen (folli- 
cles), 411, 426. : 

Amyloid Substance, its appearance, 410; 
two kinds of, the one analogous to 
vegetable starch (corpora amylacea, 
prostatic concretions), the other, more 
akin to cellulose, 411-415; their chemi- 
cal reactions, 418, 414; the latter, 
homogeneous, probably imported from 
without, 419, but independent (au- 
tochthonous) formation of in perma- 
nent cartilage, 419; not hitherto de- 
tected in blood, 419-420. 





Anzemia, occasioned by action of arte- 
ries, 151. 

Anastomosing Corpuscles, systems of. 
See Juice-conveying canals, and con- 
nective-tissue corpuscles. 

Andral, on inflammation, 429. 

Aneurysms, how produced, 155; conver- 
sion of coagula of, into homogeneous, 
cartilaginous masses, 170. 

Aorta, elastic tissue of, 135, 152; mid- 
dle coat of, 141; imperfect develop- 
ment of, in chlorosis, 261; atheroma 
of, 398-399. 

Apoplexy, from leukemia, 203; from 
capillary embolia, 244; from melane- 
mia, 257. a 

Arcus senilis, 388. 

Arnold, 53. 

Arrectores pilorum, 85. 

Arteries, distinction between small, and 
small veins, 86, 87-88; elastic tissue of 
middle coat of, 185; muscular fibre 
cells of middle coat of, 141-142; 
structure of, 141-143; epithelium of, 
146; muscular tissue of, 147-151; 
contraction of, 147-151; rhythmical 
movements of, in ears of rabbits, 147- 
148; dilatation of, not active, but 
passive, and due to fatigue of walls, 
149; fatigue of muscular coat of, 150- 
151; passive condition of, in so-called 
active hyperemia, 151; elasticity of, 
152; aneurysms of, how produced, 
153; simple fatty degeneration of, 
380, 896-397, 404; fatty usure of, 
381; atheroma of, 381-882, 394-402 ; 
sclerosis and ossification of, 403-404; 
calcification (petrifaction) of, 406-407 ; 
minute—amyloid degeneration of, 416- 
417. 

Ascherson, on stickiness of white blood- 
corpuscles, 184-185; his haptogenic 
membrane, 877. oi 


536 INDEX. 


Atheroma of Arteries, 381-382; 394-402; | Bl 
different meanings attached to term, | Bl 
394; its relation to ossification, 395- 
396, 408; false notions respecting, | Bl 
394-395; a compound process, the | Bl 
fatty metamorphosis being the second 
stage, and inflammation of the inter- 
nal arterial coat, the first, 396: to be 
distinguished therefore from simple 
fatty metamorphosis of internal coat, 
397, 404; inflammatory stage of, cor- 
responds to endocarditis, only gene- 
rally chronic, 397; concurrence of 
simple fatty change with, 897; exter- 
nal appearance of patches in early 
stage of, 397; seat of change in, 398; 
nature of deposit, 399; formation of, 
401-402; acute form of, 408-404 ; seat 
of the process in cellular elements of 
connective tissue of internal coat, 403. 

Atheromata of skin. See Epidermic cysts. 

Atheromatous ulcer, 8823; description 
of, 404. 

Atrophy, grey, of nerves, 271. 
Attraction exercised by different tissues 
upon different substances, 154, 157. 
Auditory Nerve, terminations of, in 

cochlea, 285. 


Bacillar Layer, of retina, 285, 286; of 
cerebrum and cerebellum, 801, more 
accurately described, 307-308, 

Bats, rhythmical movements in veins of 
wings of, 149. 

Baumgirtner, 53. : 

Beale, Dr. Lionel, on circulation of kid- 
ney, 424. 

Bennett, Prof., his “‘suppuration of the 
blood” (leukemia), 223. Bl 

Berend, 384. 

Bernard, Claude, on contraction of ves- 
sels from stimulation of their nerves, 
150; on dilatation of vessels from sec- 
tion of, sympathetic nerves, 150; on 
the section and irritation of nerves in 
weakened parts, 3538. 

Bichat, 28-29; his classification of tis- 
sues, 56. 

Bidder, on cells found in posterior half 
of spinal marrow, 315. 

Bile, its elements not pre-formed in 
blood, but formed in liver, 160; rela- 
tion of colouring matter of, to hema- 
toidine, 176-177. 


astema, 35-36; 54; 448-450; 548, ete. 
astema doctrine, rejection of, 489; 
449, 4517. 

ind spot in retina, 288. 

ood, little durability of cells of, 37; 
compared with muscle and nerve-fibres, 
78; seldom found as a new formation, 
92; circulation of, 141, 144; no 
transudation of, through capillary 
membrane, 144; not the real seat of 
permanent dyscrasiz, 162 ; not a per- 
manent and independent tissue, 162- 
163; origin of its dyscrasic conditions 
not to be sought for in itself, but in 
external causes, 163-165; fibrine of, 
166-170; red corpuscles of, their con- 
tents and crystals formed out of them, 
170-180 ; colourless corpuscles of, 
170-187 ; formerly regarded as inde- 
pendent fluid, 189; constantly chang- 
ing, 190; renewed by propagation in 
embryo, 190, but not even in later 
months of pregnancy or afterwards, 
1915 its corpuscular elements derived 
from lymph, 191; late coagulation of, 
its cause, 198-194; fibrinogenous sub- 
stance in, 194; late coagulation of, 
in pneumonia, its cause and its coin- 
cidence with lateness of decomposition, 
195; occasional coexistence of the 
two sorts of coagulation (early and 
late) in same blood, 195; matters found 
in, in leukemia, 205; infectamt mat- 
ters in, 245; chemical substances in, 
247-248 ; in no case permanent seat of 
definite changes, 249; extravasated, 
in fractures, of little importance in 
formation of callus, 485. 
ood-Corpuscles, Red, reason why have 
no nucleus, 37; nucleated in foetus, 
37, 78, 171, 2583; real cells; 87; 78, 
171; cannot pass through capillary 
membrane without rupture, 144; 
structure and contents of, 171; effects 
of fluids of different densities upon, 
172-174; do not contain fibrine, 174; 
crystals produced from hematine of, 
175-179 ; aggregation of, in rouleaux, 
171, 181; granular and decolorized, 
177, 215, 228; origin of, uncertain, 
258; Zimmermann’s theory of develop- 
ment of, 259; respiratory substance 
of, 265-263 ; its paralysis, 263. 





Bilharz, on distribution of nerve-fibre 
supplying electrical organ of silurus 
(malapterurus), 290, 302. 

Billroth, on nervous plexuses in submu- 
cous tissue of intestines, 291-292. 

Bladder, papillary tumours (cancerous 
oud non-cancerous) of, 513. 





Colourless, 180-187 ; 
proportion of, to red, 180; action of 
water on, 181; of acetic acid on, 181; 
their nuclei, one or several, 182-183 ; 
great resemblance of, to pus-corpus- 
cles, 181-182, 212, 527; sometimes 
visible to naked eye, 183 ; their sticki- 
ness, 184-185; in post-mortem clots, 


INDEX. 


185; in blood obtained by venssec- 
tion, 186-187; diagnosis of, from pus- 
corpuscles, 188, 527; increase in 
number of, almost constantly accom- 
panying hyperinosis, 199; increase of, 
in leucocytosis and leukzemia due to 
affection of lymphatic glands, 201, 
204, 222, and of spleen, 204; increase 
of, in scrofulosis, 226; in cancer (with 
affection of glands), typhoid fever and 
malignant erysipelas, 226. 

Blood-Crystals, 174-179. 

Body, the, as a social organization, 40. 

Boerhaave, on inflammation, 428. 

Bohm, on retention of fat in intestinal 
villi, in cholera, 369. 

Bone, organic basis of, not cartilage, 96, 
475; epithelium in, 96; found in skin 
of many animals, where in man con- 
nective tissue, 101; vessels of, 108- 
112; structure of, 109-112; nutrition 
of, 115; formation of real, in arteries, 
403-404; development of, different 
processes concerned in, 450-485; 
growth of, in length and thickness, 
451-452; fresh and living, contrasted 
with macerated, 453; formation of, 
from cartilage, 455-456, 459-461; 
caries and necrosis of, 462-464 ; lique- 
faction of, 464, 496 ; territories of, 42, 
462-464, 481; granulation of, 465-466 ; 
suppuration of, 465-466 ; formation of, 
out of medullary tissue, 466-467 ; for- 
mation of, out of periosteum (connec- 
tive tissue) 467-470, pathological, 472- 
475; development of, in rickets, 476- 
482; new formation of (callus) after 
fracture, 482-485. 

Bone-Corpuscles (cells), 109-112; real 
nucleated cells, 111-112; indirect ori- 
gin of (through marrow-cells) from 
cartilage-cells, 457; direct formation 
of, from cartilage-cells, 458-561; ter- 
ritories of (in bone formed out of 
cartilage) correspond to capsules of 
cartilage-cells out of which formed, 
462-463 ; limits of territories of, well 
.larked in caries, and necrosis, 462- 
464; formation of, from marrow-cells, 
466-467 ; from periosteal (connective- 
tissue) corpuscles, 469, 474-475 ; form- 
ation of, out of cartilage-corpuscles, in 
rickets, 479-481. 

Bone- (cell) territories, 
ries, and Bone. 

Bone-cells. See Bone-corpuscles, 

Bones, of considerable size, rgal organs, 
57; distortions of, in rickets, 477-478 ; 
see Long Bones. 

Bouchut, on pyeemia (leukemia) in puer- 
peral fever, 223. 


See Cell-territo- 





537 


Bowman, Mr. his sarcous elements, 82; 
on circulation in kidney, 424, 

Brady-fibrine, 193. 

Brain, hair in, 95; substitution, in ven- 
tricles, of simple, scaly epithelium for 
ciliated, 100 ; sudden occlusion of ves- 
sels in, 244; yellow softening of, 
merely fatty degeneration, 888; im- 
port of pigment-cells in, 388; solitary 
tubercles of, 523-524; see Cerebrum. 

Bright’s disease of the kidney, 835; 
389-390; 392; large proportion of 
cases of, due to amyloid degeneration, 
422; three forms of (parenchymatous 
nephritis, amyloid degeneration, inter- 
stitial nephritis), 424, possible coexist- 
ence of two, or all three of them, 424. 

Brood-cavities (physalides) 444-445. 

Broussais, on inflammation, 428, 429. 

Brown, Robert, on nuclei of vegetable 
cells, 32. 

Brown-Séquard, 420. 

Brucke, 80; on optical properties of 
different constituents of primitive 
fasciculi of muscle, 82; on striated 
border of cylindrical epithelium of in- 
testinal villi, 367 ; on muscular fibres 
of intestinal villi, 367. : 

Bubo, syphilitic, seat of virus in, 221. 

Buffy coat, 186; in inflammations of 
respiratory organs (pneumonia, pleu- 
risy), 193; due to presence of fibrino- 
genous substance in blood, 194, 


Calcareous metastases, 248-249, 

Calcareous salts, 170; metastases of, ° 
248-249. 

Calcification, of arteries (petrifaction), 
its course described, 407; distinction 
between, and ossification, 407; of car: 
tilage, 455, 458-460; irregularity of, 
in rickety bones, 476. 

Callus, formation of, 482-485. 

Canaliculi of Bone, 111; cannot be in- 

_ jected from Haversian canals, 115 ; 
no real existence in living bone, in 
which completely filled up by pro- 
cesses of bone-cells, 461. 

Canaliculi chalicophori, 111 

Canaliculi of teeth, 115. 

Cancer, supposed specific nature of, 90 ; 
existence of physiological type for, 
91, ef. 529; lymphatic glands in, 221 ; 
rapidity of propagation of, dependent 
upon greater or less abundance of 
parenchymatous juices in, 252, 580; 
two possible modes of propagation of, 
252; its metastases follow direction of 
secreting organs, 253, cf. 505; propa- 
gation of, probably due to certain 
fluids, 254; irregularity observed in 


538 


metastasis of, thus explained, 253; en- 
dogenous cell-formation in, 444-445 ; 
in bone, formed by direct transition 
out of osseous tissue, 453-454 ; corre- 
spondence between first stage of, and 
that of pus, 499; development of, from 
connective tissue, 499; papillary (vil- 
lous) form of, 512-513; cells of, how 
distinguished from those of tubercle, 
521; cheesy metamorphosis of, 524 ; 
proper, malignity of, 529-530. 

Cancer Aquaticus, 517. 

Syphiliticus, 517. 

Cancer-Juice, compared with pus, 91. 

Cancroid, correspondence between first 
stage of, and that of pus, 499, 527- 
529; malignant nature of, 529, its de- 
gree, 530. 

Capillary Arteries, 87; fat in external 
coat of, 87, 143, pigment in do., 148. 
Capillary Blood-vessels, 355; structure 
of, 87; non-contractility of, 87; of 
liver, 102-104; of cerebrum (corpus 
striatum), 104-105; of muscular coat 
of stomach, 105-106; in cartilage of 
new-born child, 107-108; membrane 
of, supposed to be equivalent to inter- 
nal coat of arteries, 143, its importance 
in nutrition, 153; sluggish layer in, 

185. 

Capillary Membrane, complete absence 
of pores in, 144; its importance in nu- 
trition, 153-154. 

Carbonic Oxide, paralyzing effects of, on 
respiratory substance of red blood- 
corpuscles, 262. 

Caries, course of, 463-464; changes (de- 
structive or developmental) of bone- 
cells in, 463, 465; liquefaction of 
bone-(cell) territories in, 464; a de- 
generative ostitis, 464; production of 
granulations in, 465. 

Caries of vertebree. See Spondylar-thro- 
cace. 

Carter, Dr., on excretion of starch 
through skin, 420. 

Cartilage, corpuscles and cells of, 82-33; 

41; proliferation of cells of, 48; hya- 

line, 73; fibro-, 74; reticular (yellow 

or spongy), 74; non-vascularity of 
perfectly developed, 89, 107; not or- 
ganic basis of bone, 95, 475; vessels 
in, in new-born child, 106-108; nutri- 
tion of, in new-born child, 107 ; effects 
of irritation upon (nutritive irritation 
of), 335-336 ; permanent—autochtho- 
nous formation of amyloid substance 
in, 419; proliferation of, when pre- 

paring for ossification, 448, 455-456, 

sensitiveness of cells at that time, 

455-456; transformation of—into mar- 








INDEX. 


row, direct, 457-459, indirect (through 
osseous tissue), 457—into bone, indi- 
rect (through marrow), 457, direct, 
458-460; calcification of, 456, 458- 
460; formation of, out of periosteum, 
469, 483; rarity of malignant affections 
in, and its cause, 504. 

Cartilage-Cells, structure of, 32-33; pro- 
liferation of, 48, during ossification, 
443, 454; transformation of, into 
marrow-cells, direct, 457-459, indirect 
(through bone-cells), 457—into bone- 
cells, indirect (through marrow-cells), 
457, 465-466, direct, 458-461; throw 
out processes (become jagged) during 
ossification, 461. 

Cartilage-Corpuscles, structure of, 33; 
definition of, 458-460 ; conversion of, 
into bone-corpuscles, in rickets, 479- 
482. 

Cataract, production of, in frogs by in- 
jection of salt, 154. 

Cauliflower Tumours, of penis and neck 
of uterus, 514. 

Cell-contents, importance of, in deter- 
mining functions of parts, 39; func- 
tions of parts due to minute changes 
of place in, 327. 

Cells, ultimate active elements of living 
body, 29; theory of formation of, out 
of free blastema, 35-36; as vital uni- 
ties, 39; territories of, 40-41, see Cell- 
territories; difference in size of, 48- 
50; proliferation of (cartilage), 48; 
origin of all developed tissues, 55; 
increased absorption of matter by, 
336, &c. ; intra-capsular multiplication 
of (in intervertebral cartilage), 349; 
division of, 349-350, see Division of 
cells; new formation of, by means of 
simple division, 443-444, endogenous 
(brood-cavities), 444-445, hyperplastic 
(direct and indirect), and heteroplas- 
tic, 446-448. 

Animal, 32-50; capsulated (car- 

tilage), 32-33 ; simple, 84; nucleus of, 

34-88 ; nucleus of, 35-36 ; contents of, 

38-39. 

Vegetable, 30-32, 45-47; capsule 
and membrane of, 30-31; contents of, 
30-31; nucleus of, 32; growth of, 46- 
47. 

Cell-Territories, 40-41, 114, 124; in skin, 
281-282 ; limits of, in bone, well-shown 
in caries and necrosis, 462-464; of 
bone, 481. 

Cell-theory, 36, 89. 

Cellular districts. See Cell-territories, 

Cellular Elements, activity and excita- 
bility (irritability) of, 324-325; in- 
creased quantity of material taken up 








INDEX. 


by when irritated, 336, &c.; anasto- 
mosing, of tissues, importance of, in 
conveyance of infection, 504-505. 

Cellular Pathology, contrasted with Hu- 
moral and Solidistic, 40-42, 162, 504 
et passim. See Humoralism and So- 
lidism, 

Cellular Tissue. See Connective Tissue. 

Cellulose, reaction of, with iodine and 
sulphuric acid, 31, similar to that of 
cholestearine with same reagents, 400, 
414; analogy of, to amyloid substance, 
414. 

Cerebellum, bacillar layer of, 301, 307- 
308. ry 

Cerebrum, bacillar layer of, 301, 807- 
308; ganglion-cells of, 295, 298-299 ; 
see Brain. 

Chanere, 500, 517. 


. Cheesy metamorphosis, of pus, 218-215 ; 


of tubercle, 522 524; of cancer, 524; 

. of sarcoma, 524. 

Chlorosis, 260-261; distinction between, 
and leukemia, 261; imperfect deve- 
lopment of different organs in, 261; 
congenital, or coming on in early 
youth, 261. _ 

Cholepyrrhine, allied to Hematoidine, 


Cholera, leucocytosis in, 228 ; retention 
of fat in intestinal villi in, 369. 

Cholestearine, in atheromatous deposits, 
382, 399-400; its reaction with iodine 
and sulphuric acid, 400, similar to 
that of cellulose with the same re- 
agents, 400, 414. 

Cholesteatoma, 528. 

Chyle, absorption of, 367, 368 ; retention 
of, 369. 


Ciliary movement, persistence of, after - 


death, 331; provoked by soda and 
potash, 331. 

Classification, of normal tissues, the au- 
thor’s, 55, Bichat’s, 56; of pathologi- 
cal new-formations, 91-92, 508-510. 

Cloudy Swelling, 335; in cornea, 344; 
in kidney and muscle, 392; &c. 

Club-foot, fatty degeneration of muscles 
in different kinds of, 384. 

Cochlea, terminations of auditory nerve 
in, 285; bodies found in, allied to 
corpora amylacea, 319-320. 

Colloid, definition of the term, 510-512 ; 
different forms ef, 525-526. 

Collonema, 526. 

Colostrum, 376-377 ; compared with se- 
baceous matter, 376, with milk, 377. 
Condylomata, acuminate (non-syphilitic) 

and broad, flat (plaques muqueuses— 
syphilitic), 282, 512. 
Connective substance, 98. 





539 


Connective Tissue, 69-70; fibres of, 69- 
70, 138; Reichert’s theory of forma- 
tion of, 70-72, Henle’s, 71-62, 
Schwann’s, 71-72, the author’s, 71-72; 
nutrition of, 131; interstitial, in mus- 
cles, 181; loose, in dartos, 136-137 ; 
structure of, 137-189 ; resemblance of 
intercellular substance of, to fibrine, 
169; action of vegetable, and diluted 
mineral acids upon, 169; of intestinal 
villi, 366-367 ; and its equivalents, 
common stock of germs of body, 441; 
general source of pathological new- 
formations, 441; transformation of, 
into osteoid tissue and bone, 467-469, 
472-475 ; formation of callus out of, 
483-484; development of pus out of, 
495; development of cancer out of, 
499, of tubercle out of, 522, of sarcoma 
out of, 531. 

Connective-Tissue Corpuscles, 35, 72-78, 
138; at base of papille in corium, 61, 
277; anastomosing systems of, a sup- 
plement to blood- and lymphatic ves- 
sels, 79, in bone, 111-112, in teeth, 
115, in semilunar cartilages, 116-117, 
in tendons, 121-124, in cornea, 125, 
342-344, in umbilical cord, 130, in dar- 
tos, 136, 137, in melanotic tumour from 
parotid gland, 346, in periosteum, 
468, 473; proliferation of (in suppu- 
ration) in interstices of muscle, 489, 
in subcutaneous tissue, 495-496, in 
development of cancer, 499, in deve- 
lopment of tubercle, 521, in develop- 
ment of sarcoma, 531. 

Connective Tissues, 69-76; connective 
tissue proper, 69-72; cartilage, 74-75; 
mucous tissue, 75; reticular arrange- 
ment of cells in (connective tissue, 
bone, mucous tissue, &c.), 76; its ob- 
ject, 76; kind of neutral ground, 99; 
strictly speaking, scarcely any real 
function, 327; source of nearly all 
new-formations, 441. 

Connective-Tissue Tumours. See Fibrous 
Tumours. 

Consciousness, 323-324. 

Contagious Juices, infection by means 
of, 254, 504-505. : 

Continuity of Tissues, law of (Reichert’s), 
97-99. 

Continuous Development, law of, 54-55; 
in opposition to blastema and exuda- 
tion doctrine, 439. 

Contractility, of muscle, 81, 84-85; of 
arteries, 147. 

Contraction, of muscle, 81-82; of arte- 
ries and its effects, 147-151. Seep. 85. 

Cord, umbilical. See Umbilical cord. 

Corium, 60, 62; papillary portion of, 


540 


1353; elastic networks of, 135-1386, 
277. 

Cornea, nutrition of, 116, 125; vessels 
of, 125; inflammatory opacity of (ke- 
ratitis), 840-341, 843-344, may termi- 
nate favorably, 344 ; structure of, 342, 
348. 

Corpora Amylacea, 318, 318-320; where 
chiefly found, 318-319; reactions of, 
820; nature of, 411-412; analyses 
(Schmidt’s) of, 415; confounded with 
sabulous bodies found in choroid plex- 
uses, 415; said in one instance to have 
been found in blood, 419. 

Corpora Lutea, formation of, 386-387 ; 
difference between puerperal and men- 
strual, 386. 

Corpus Striatum, arrangement of capil- 
laries in, 104-105. 

Corpuscules Tuberculeux, 518, 520, 526. 

Counter-irritation, its effects explained, 
ok, 

Crasis, Phlogistic, dependent upon local 
inflammation, 195; its connection with 
lymphatic vessels, 196; not met with 
in inflammation of the brain, 196. 

Creatine, in smooth muscular fibres of 
uterus, 84. 

Crell, on ossification of vessels, 896. 

Croup, exudation in, generally first mu- 
cous, then fibrinous, 434. 

Crusta granulosa, 187. 

Crusta phlogistica. See Buffy coat, 186. 

Cruveilhier, on phlebitis, inflammation, 
&c., 231, 282, 237; his tumeur perlée, 
528. 

Crystalline Lens, See Lens. . 

Curvature, lateral and posterior (angu- 
lar), fatty degeneration of longissimus 
dorsi in, 384-385. 

Cuticle. See Epidermis. 

Cutis. See Corium. 

Cyanosis, acute and chronic, 372. 

Cysts, so-called purulent, in heart, 237- 
288 ; sebaceous (epidermic), see these 
words. 

Cytoblastema, 35-36, 54, 67, 493. 

Czermak, on the preservation of tissues 
in mummies, 3265. 


Dartos, 136-137. 

Degeneration, composed of active and 
passive processes, 357 ; fatty, 359-406 ; 
amyloid, 409, 427; see special names. 

Denis, on presence of fibrine in blood- 
corpuscles, 174. 

Descemet, Membrane of, 341. 


Destructive Processes, 488; connection. 


between, and processes of growth, 498. 
Diarrhoea, in amyloid degeneration of 
intestines, 421. 





INDEX. 


Dieffenbach, 514. 

Diffuse phlegmonous (pseudo-erysipela- 
tous) inflammation, hyperinosis and 
leucocytosis in, 200. 

Dipolar state of nerves. See Electrotonic 
state of nerves. . 
Distortions, fatty degeneration of mus- 

cles in, 384. 

Division of Cells, in red blood-corpuscles 
in foetus, 258; in lymph-corpuscles, 
212; in intervertebral cartilage, 399 ; 
from direct irritation, 849-350 ; most 
common mode of origin of new-forma- 
tions, 445; sometimes delayed for a 
long time, 446; in pus (uncertain), 
446; in development of cancer, 449, 
of tubercle, 521, of sarcoma, 531; et 
passim. 

Division of Nuclei, in muscle, 79, 81; in 
colourless blood-corpuscles, 180-181 ; 
in lymph-corpuscles, 208 ; in pus-cor- 
puscles, 213, 446; in formative irrita- 
tion, 345-3848 (marrow, 846, muscle, 
346-348); in development of cancer, 
499, of tubercle, 521, of sarcoma, 531; 
et passim, 

Division of Nucleoli, in formative irrita- 
tion, 345. 

Donders, on conversion of cells of con- 
nective, into elements of elastic, tis- 
sue, 181. 

Donné, his corps granuleux, 877. 

Drunkard’s dyscrasia, 162. 

Dubois-Reymond, his experiments or. 
electrical silurus, 290; on activity of 
nerves even when seemingly at rest, 
325. 

Duhamel, on development of bone, 452; 
on periostitis, 468. 

Dyscrasiz, their local origin, 162-164; 
two great categories of, 166-167; ex- 
ample of local origin of, afforded by 
hyperinosis, 199; seat of, never in 
blood, but always due to changes in 
some organ or organs, 251. 


Kctasis of arteries and veins, 158. 

Edwards, Milne-, his globule theory, 52. 

Elastic Tissue, 182-136 ; its fibres formed 
out of cells of connective-tissue, 132 
1384; arrangement of fibres in, 132; 
its extraordinary power of resisting 
reagents, 133; probably small central 
cavity in fibres of, 133; in corium, 
132-136, 277; in middle coat of arte- 
ries, 135, 152; in aorta, 135, 152; in 
veins, 144, 152. 

Elasticity of Arteries, its influence upon 
current of blood, 152. 

Electrical organ of fishes (Silurus), plexi- 
form distribution of uerve-fibres in, 





INDEX. 


290; nerves of, all derived from one 
ganglion-cell, 301. 

Electro-tonic (dipolar) state of nerves, 
§ 28. 

Elements of tissues, their specific action, 
161. 

Emboli, 240-244; retrograde metamor- 
phosis of, 241; gangrenous softening 
of, 242. 

Embolia, 238-244; from thrombosis in 
veins, 233-240 ; from endocarditis, 248, 
405-406 ; capillary, 244. 

Embryo, formative cells of, difference in 
size and in time required for develop- 
ment, 448. 

Empyema, inspissation of pus in, 215. 
Enchondroma, a heteroplastic tumour, 
95-96 ; occasional malignity of, 531. 

Endoarteritis, 402-408. 

Endocarditis, not unfrequently cause of 
embolia, 243; its analogy to atheroma 
of arteries, 397, 404-405; description 
of its course, 405. 

Endogenous cell-formation, 444-445; a 
rare mode of origin of new-formations, 
445. 

Endosmosis, 153. 

Ependyma, of ventricles of brain, $11- 
814; original, and extended definition 
of, 311-312; strictly speaking not a 
membrane, 812-313; central thread 
of, in spinal cord, 305, 315. 

Epidermic Cysts, 381, 895. 

——— Globules, in epithelial cancer 
and pearly tumours, 528, 580. 

Epidermis, 57, 59-61; formation of crys- 
talline lens from, 65, of pigment-cells 
from, 66; in muscular substance of 
heart, 95 ; substitution of, in prolapsed 
vagina for soft epithelium, 100; for- 
mation of pus in, 491-492. 

Epithelial Cancer. See Cancroid. 

Epithelial Cells, formation of glands from, 
66, 67; relation of, to mucus- and pus- 
corpuscles, 493-494. 

Epithelial (epidermic) tumours, in lym- 
phatic glands, connective tissue and 
bone, 95. 

Epithelioma. See Epithelial cancer, and 
Cancroid. 

Epithelium, ciliated: substitution of 
squamous epithelium for, in ventricles 
of brain, and also in uterus in preg- 
nancy, 100; movements of cilia unex- 
plained, 829; provoked by soda and 
potash, 331. 

cylindrical, 58; connection of, 

with connective tissue corpuscles, 98, 

with nerve-fibres, 98 ; of villi, 365-366 ; 

of gall-bladder and biliary ducts, 58, 

870. 








541 


Epithelium, formation of pus in, 489-490, 

——— of arteries, 145, 

—— — of veins, 145. 

of vessels of kidney, 145. 

pulmonary, pigmentary and fatty 

degeneration of, 387. 

renal, fatty degeneration of, 389. 

scaly, distinctly separated from 
connective tissues, 99. 

—-—— transitional, 58-59. 

Erasistratus, 359. 

Erysipelas, hyperinosis and leucocytosis 
in, 200. 

Exanthemata, acute, leucocytosis in, 
without any considerable formation of 
fibrine, 200. 

Excitability. See Irritability. 

Exosmosis, 153. 

Exudation, inflammatory, great part of 
what called due to activity of elements 
of tissues, 429; both mucous and 
fibrinous, each confined for most part 
to certain tissues, 432-435; no exist- 
ence in usual sense of term, 436; 
non-occurrence of, in periostitis and 
formation of callus after fracture, 468. 

parenchymatous, 339-340. 

Exudation-corpuscles. See Granule-glo- 
bules, 

Exudation doctrine, rejection of, 438- 
439. 

















Fat, structure of, same as that of con- 
nective tissue, 76; the three aspects 
under which it appears, 860-362 ; 
structure and retrogressive metamor- 
phosis of, 362-363 ; transitory infiltra- 
tion with (villi, liver), 8365-374; seat 
of, in acini of liver (fat-zone), 372; 
accumulation of in, and re-absorption 
of from, marrow-cells, 458. 

Fatigue, of muscular coat of arteries, 
148, 149-150; result of functional ac- 
tivity, 330. 

Fatty Degeneration, of pus-corpuscles, 
216; general view of, 359-360; of 
muscles, interstitial and intrinsic, 363- 
365 ; of heart, 365, 383-384, from ex- 
cessive dilatation of its cavities, 393- 
394; of liver, 370-374; of cells of 
sebaceous glands, 875; of cells of 
mammary gland, 376-377 ; of arteries, 
880; of muscles, 384-385; of corpora 
lutea, 386-387; of pulmonary epithe- 
lium, 348; of renal epithelium, 388- 
890; primary and secondary, 391; 
secondary (inflammatory) nearly al- 
ways preceded by cloudy swelling, 
892-393 ; similarity of result in non- 
inflammatory and inflammatory kind, 
393; of substance of heart from ex- 


542 


cessive dilatation of its cavities, 392- 
394 ; simple—distinction between, and 
atheroma, 404; simple, superficial and 
deep, of valves of heart, 404-405. 

Fatty Infiltration, transitory (villi, liver), 
865-374. 





Metamorphosis. See Fatty Dege- 
neration. 
—— Tumours, 363. 
—— Usure, 381. 


Fibres, undue prominence assigned to, 
52. 

Fibrine, really one of specific constitu- 
ents of blood, 167; its fibrille, 167- 
170, compared with those of mucus, 
168, with those of connective tissue, 
169, fibrillar stage of, always preceded 
by homogeneous one, 168; in aneu- 
rysmal coagula, 170 ; notion, that con- 
tained in red blood-corpuscles, erro- 
neous, 174; coagulation of, giving 
rise to buffy coat, 186; of lymph, how 
it differs from that of blood, 192; not 
formed in blood, but in tissues, 196- 
198, 485; exudation of, never result 
of pressure, 197, 435; but always due 
to irritation, 197; no evidence that 
produced by transformation of albu- 
men, 197 ; see Hyperinosis and Hypi- 
nosis. 

Fibrinogenous substance, in pleuritic 
fluids, 192-193; in lymph, 198; in 
blood of peripheral veins, 198; in 
fluid of blisters raised by cantharides- 
plasters, 198. 

Fibro-cartilage, nutrition of, 116. 

Fibro-plastic Tumours, 509. 

Fibrous Tissue, definition of, 581. 

Fibrous Tumours, of Uterus, 487, 516- 
517, 526; occasional conversion of, 
into sarcomata, 532-533. 

Fifth Pair of Nerves, effects of section 
of, explained, 350-351. 

Flourens, on growth of bones, 569. 

Focus, definition of, 502; cf. 881, note 
on Heerd. 

Follicles, of lymphatic glands, 207-209 ; 
of intestines (solitary and Peyerian) 
and of root of tongue, really lymphatic 
glands, 226-227. 

Formative Irritation, 344, often conjoin- 
ed with nutritive irritation, 344 ; divi- 
sion of nucleoli in, 345, of nuclei, 345- 
347, of cells, 349-350. 

Formic acid, in leukemic blood, 205; in 
spleen, 205. 

Fox, Dr. Wilson, on fatty usure of gas- 
tric mucous membrane, 381. 

Fractures, formation of callus in, 482-485. 

Frérichs, on melanzemia and its results, 
257. 





INDEX. 


Friedreich, on occurrence of laminated 
bodies in lungs, 412. 

Fripp, Dr., 425. 

Frog, ova of, 48-49 ; irregular contrac- 
tion of vessels in web of foot of, 149. 

Fuchs, his new name for tubercle, 510. 

Function, lesion of, an accompaniment 
of inflammation, 430. 

Functional Activity, impairment of (fa- 
tigue), through long continuance, 330. 

Irritability, 327-333. 

Irritation, 830-331. 

— Restitution, 330. 

Funke, on Hemato-crystalline, 179, 











Galen, 28; 3839; on inflammation, 428. 

Gall-bladder, epithelium of, 58, 370. 

Ganglion-cells, deposition of pigment in, 
294-296; very rarely round, almost 
always branched, 296; three different 
kinds of (motor, sensitive, sympathe- 
tic) in spinal marrow (horns), 296-300 ; 
three categories of processes of, 301 ; 
in cortex of cerebrum and cerebellum, 
298, 299, 807, 308; in spinal marrow 
of Petromyzon fluviatilis, 308, 309. 

Ganglionic apparatuses, 294; see Ner- 
vous Centres. 

Gangrene of Lungs, from gangrenous 
metamorphosis of thrombus in trans- 
verse sinus, 387, cf. 241. 

Garrod, Dr., his able method for the 
detection of urates in the blood, 248. 

Gastric (so-called) inflammations, secre- 
tion in, 438. 

Gelatinous degeneration, of nerves, 271; 
of spinal cord, 319-320. 

Generation, equivocal or spontaneous, 
non-existence of, 54, &e. 

Gerlach, on ganglion-cells met with in 
spinal cord, 299; on disposition of 
nerves in cortex of cerebellum, 307. 

Gland-cells, essential elements of glands, 
68 ; locomotory effect produced by, 
329. 

Glands, active elements of, essentially 
of epithelial nature, 67; development 
of (sudoriferous, sebaceous, mammary, 
stomach-, liver), 68-69 ; uni-cellular, 
67; object of transuded fluid in, 68; 
lymphatic, 78, 205-210; lymphoid, 
226-228 ; salivary, Ludwig’s researches 
on, 329. 

Globes épidermiques, 528, 530. 

Globules, elementary, false notions re- 
specting, 52; laminated, see Epidermic 
globules, 

Globules, inflammatory. See Inflamma- 
tory globules. 

Gluge, his inflammatory globules, 378. 

Gobley, on lecithine (myeline) 270. 


INDEX. 


Goodsir, Prof., on nuclei, 349. 

Gout, metastatic deposits in, 248. 

Graefe, 247, 840, on parenchymatous 
keratitis, 345. 

Granulation of bone, 465. 

Granulations, close correspondence be- 
tween, and medullary tissue, 465; 
transformation of, into pus, 465-466 ; 
starting-point of all heteroplastic de- 
velopment, 470; formation Of, in sup- 
puration of connective tissue, 497. 

Granule- (Fat-granule-) Cells, 377-378 ; 
diagnosis between, and pigment-cells, 
387-388. 

Granule Globules [exudation-corpuscles], 
879, 391; in atheromatous deposits, 
392. ; 

Granules, elementary, 47. 

Growth, connection between, and de- 
structive, heteroplastic processes, 498. 

Giterbock, on pus-corpuscles, 181. 


Hematine, 171; three kinds of crystals 
derived from, 174; hematoidine, 175- 
177; hemine, 177-179 ; hemato-crys- 
talline, 179-180. 

Hemato-crystalline, 179-180; very per- 
ishable, 179, affected by oxygen and 
carbonic acid in same way as hema- 
tine, 180. 

Hematoidine, 175-177 ; spontaneously 
formed from hematine, 175; crystals 
extremely minute, 175; formation of, in 
apoplectic clots and Graafian vesicles, 
176 ; allied to colouring matter of bile, 
177. 

Hematuria, from papillary tumours of 
bladder, 513. 

Hemine, 177-179; not a spontaneous 
product, 177; of great importance in 
forensic medicine, 178-179. 

Hemitis, Piorry’s doctrine of, 187, 228. 

Hemorrhage, cannot occur by transuda- 
tion (per diapedesin) without rupture, 
144, 

Hemorrhagic diathesis, its origin often 
to be sought for in spleen or liver, 
164; in leukemia, 203, 

Hair, in brain, 95. 

Hair-follicle, with sebaceous glands, $75. 

Haller, importance assigned to fibres by, 
52; on irritability, 332; on ossifica- 
tion of vessels, 396; on atheroma, 398. 

Hannover, on epitheliomata, 527. 

Haptogenic Membrane, 377. 

Harting, G., on vesicles found as artifi- 
cial products in blood, 259; on secre- 
tion of liver after section of its nerves, 
332. 

Havers, on development of long bones, 
451, 452. 





543 


Haversian canals, 108-110; their con- | 
nection with bone-corpuscles, 114-115. 

Heart, so-called purulent cysts of, 287- 
238; inflammation of valves of, 243, 
404, 405 ; fatty degeneration of, two 
kinds, 365, from excessive dilatation 
of its cavities, 393-394, of valves of, 
404, 405. 

Heerd, definition of, 381; ef. 502. 

Heidenhain, Junr., on epithelium of in- 
testinal villi, 367. 

Henle, on transitional epithelium, 59; 
his theory of the formation of connec- 
tive tissue, 70-71; on lining membrane 
of cerebral ventricles, 310; on deve- 
lopment of mucus- and pus-corpuscles 
on mucous membranes, 448, 449. 

Hepatic Artery, supplies branches to 
capillary network of acini of liver, 
104; amyloid degeneration of termi- 
nal ramifications of, 418. 

Hepatic Cells, arrangement of, and rela- 
tion to capillaries of liver, 103; really 
active elements of liver, 158; absorp- 
tion of fat by, 159; formation of sugar 
by, 160; accumulation of fat in (fatty 
degeneration), 372; amyloid degene- 
ration of, 418-419. 

Hepatitis, no fibrine found in genuine, 
390. 


- Heteradenia, 90. 


Heterochronia, 92. 

Heterologous New-formations, not ne- 
cessarily malignant, 92, 529; developed 
with great rapidity, 449 ; granulations 
the starting-point of, 470; definition 
and examples of, 486-488; develop- 
ment of, similar to that of pus, 499; 
parasitical nature of, 505-506; physi- 
ological types of, 525; infectiousness 
of, according to amount of juice, 252, 
530-5381. 

Heterology, definition of, 92-93, 96; not - 
to be confounded with malignity, 92, 
529. 

Heterometria, 92. 

Heteroplasia, see Heterology, contrasted 
with Hyperplasia, 95-96 ; a rapid pro- 
cess, 449. 

Heterotopia, 92. 

His, on structure of cornea, 342, 348. 

Histological Equivalents, 99-100. 

Histological Substitution, 99-100; how 
it differs from pathological substitu- 
tion, 100. 

Histology, General, 56; Special, 56. 

Homologous New-formations, definition 
of, 93, 486-487 ; usually included under 
the terms Hypertrophy, Hyperplasy, 
93. 


Hoppe, on effects of carbonic oxide upon 


544 


respiratory power of red blood-corpus- 
cles, 262. , 

Humoralism, 43-44; 157; 
339; 349-350; 504, 533. 

Hunter, John, on development of ves- 
sels in pathological formations, 89 ; 
on secretion of pus from walls of veins 
in phlebitis, 231; his division of in- 
flammations, 437, 

Huxley, Prof., connection between ten- 
don and muscle, 99. 

Hydrogen, cyanuretted and arseniuret- 
ted, their action upon respiratory sub- 
stance of red blood-corpuscles, 262. 

Hyperemia, so-called active, vessels in, 
in passive condition, 149-151; has no 
directly regulating influence upon nu- 
trition of tissues, 155; produced by 
section of sympathetic in the neck, 
156. 

Hyperinosis (increase of fibrine in blood) 
dependent upon local inflammation 
and not due to changes in constituents 
of blood, 195; generally dependent 
upon inflammation of organs well sup- 
plied with lymphatic vessels and con- 
nected with large masses of lymphatic 
glands, 195; not met with in inflam- 
mation of brain, 196; when consider- 
able almost always accompanied by 
increase in number of colourless blood- 
corpuscles, 199; in erysipelas, diffuse 
phlegmonous (pseudo-erysipelatous) in- 
flammation, 200-201; in pregnancy, 
225. 

Hyperplasia, distinguished from Hyper- 
trophy, 98-94, 445-446; contrasted 
with Heteroplasia, 95-96; a rather 
tardy process, 449. 

Hypertrophy, distinguished from Hyper- 
plasia, 93-94; simple, scarcely to be 
distinguished from results of nutritive 
irritation, 3386. 

Hypinosis (diminution of quantity of 
fibrine in blood) in fevers of typhoid 
class, 200. 

Hypoxanthine, in leukemic blood, 205; 
in spleen, 205. 


160; 283; 


Ichorrhemia, 250-251. 
504-505, 529-530. 
Induration, a form of (passive) degene- 
ration, 359. 

Infection, by means of contagious juices, 
254, 504-505. Cf. 252, 529-530. 

Inflammation, its course in previously 
hyperemic tissues, 156; diffuse phleg- 
mounous, hyperinosis and leucocytosis 
in, 200; part of what is ordinarily 
called, included in nutritive irritation, 
335 ; neuro-paralytical (resulting from 


Cf. 252, 264, 





INDEX. 


abolition of action of nerves by seo» 
tion, &c.) done away with, 351-353; a 
compound of the three forms of irrita- 
tion (functional, nutritive, formative), 
354 (but cf. 431); no longer to be 
considered as a real entity, 427; each 
of its four cardinal symptoms (heat, 
redness, swelling, pain) in its turn re- 
garded as the essential one, 428-429; 
irritation, starting-point in every form 
of, 429, 430; cannot occur without an 
irritating stimulus (irritament), 429; 
Jesion of function, an accompaniment 
of, 480; in every case begins with an 
increased absorption of matters into 
the tissue, 481, not dependent upon 
hyperemia, may occur both in vascu- 
lar and non-vascular parts, 432; exue 
dation in, both mucous and fibrinous, 
4533; two forms to be distinguished, 
the purely parenchymatous (where no 
exudation) and the secretory (exuda- 
tive), 486, occurring for the most part 
in different organs, and the former 
more serious than the latter, 436-437. 

Inflammatory Globules (see Granule- 
globules), 379; 391. 

Inflexion, of bones, in rickets, 477. 

Infraction, of bones, in rickets, 477. 

Intercellular substances, division of, into 
districts, territories (cell-territories), 
40-41. - 

Intermittent fever, melanemia in, 256- 
257; melanic corpuscles in blood in, 
260; see Ague. 

Interstitial Nephritis, 424. 

Intestines, solitary follicles of, equivas 
lent to follicles of lymphatic glands, 
226, 227; nervous plexuses in sube 
mucous tissue of, 291-292; amyloid 
degeneration of, giving rise to defi- 
ciency of absorption and diarrnwa_ 
4215 suppuration in mucous mem- 
brane of small, 492-493. 

Investment-theory, 53. 

Iodine, action of (alone and with sul- 
phuric acid) on cellulose, 31, on cor- 
pora amylacea of brain, 320 (cf. 413); 
on cholestearine, 400 ; (alone) on amy- 
loid prostatic concretions, 413; on 
amyloid substance, (alone and with 
SO,), 422, 427. 

Irritability, criterion of life, 8325; fune- 
tional (nerves, muscles, ciliated epi- 
thelium, glands), 327-833 ; muscular, 
independent of nerves, 833; nutritive, 
334-345, 

Irritament, definition of, 480, 481. 

Irritation, increased absorption produced 
by, 155; influence in producing in- 
creased nutrition, 157; essential for 


INDEX. 


the production of every vital action, 
825; results of, either functional, nu- 
tritive, or formative, 326-327; func- 
tional, 880; nutritive, 334-345; for- 
mative, 345-350; inflammatory, a 
compound phenomenon, 354; the 
starting-point in every form of inflam- 
mation, 4380-431; definition of, 431. 
Ischeemia, result of action of arteries, 151. 


Jacubowitsch, on the presence of a gang- 
lion-cell in the bulbous swelling in 
which the nerve of a Pacinian body 
terminates, 276; on the three kinds 
of ganglion-cells met with in the 
spinal cord, 297, 298, 315. 

Jauche (sanies) definition of, 500. 

Jelly of Wharton, 126; its close rela- 
tionship to vitreous body, 129. 

Jones, Mr. Wharton, on rhythmical move- 
ments of veins of bat’s wing, 148; on 
irregular contraction of small vessels 
in frog’s web, 149. 

Juice-conveying Canals or Tubes, in pa- 
pille of skin, 62, 277; a supplement 
to blood- and lymphatic vessels, 76 ; 
in bone, 115; in teeth, 115; in semi- 
lunar cartilages, 116; in cornea, 116; 
in tendon, 120-124; in umbilical cord 
(mucous tissue), 180-181; in dartos, 
186-187; in connective tissues, 131; 
in connective tissue-proper, 138; see 
346, 504. 

Taices, conveyance of infection by means 
of morbid, 257, 504-505. Cf 254, 
530-531. 


Kekule, his analysis of amyloid spleens, 
415. 

Keratitis 
843-344, 

Kidney, epithelium of vessels of, 145 ; 
action of, due to its epithelium, 158 ; 
minute metastatic deposits in, from 
endocarditis, 244; swelling of, and 
changes in, from infectant matters in 
blood, 246; deposition of silver in 
Malpighian bodies and medullary sub- 
stance of, 247; deposition of urate of 
soda in, in gout, 248; changes in, in 
Bright’s disease, 335-836 ; appearance 
of convoluted tubules in fatty degene- 
ration of, 389; inflammatory (second- 
ary) fatty degeneration of epithelium 
of (392), leading to atrophy, 393; 
amyloid degeneration of Malpighian 
bodies of, with their afferent arteries, 
423; circulation in, 424. 

Kirkes, Dr., 406. 

Kluge, on independent vascular system 
of new-formations, 89. 

35 


(parenchymatous), 840-341, 





545 


Kolliker, 67, 68; on contractile sub- 
stances of muscle, 85; on muscular 
fibres of umbilical vessels, 127; on 
Hemato-crystalline, 179; on lympha- 
tic glands, 207; on many-nucleated 
cells in marrow of bones, 347; on 
striated border of cylindrical epithe- 
lium of intestinal villi, 866-367; on 
physiological fatty liver in sucking 
animals, 370. 

Kunde, on production of cataract in 
frogs by introduction of salt into in- 
testinal canal or subcutaneous tissue, 
154; on Hemato-crystalline, 179. 


Lactic acid, in leukemic blood, 205; in 
spleen, 205. 

Lacune, no real existence in living bone, 
in which entirely filled up by bone- 
cells, 458-460 ; see Bone. 

Laennec, on colloid, 510-511, 525; on 
tubercle, 517, 519. 

Lardaceous (Bacony) Degeneration. See 
Amyloid Degeneration. 

Lebert, his fibro-plastic corpuscles, 70- 
71; on the corpuscles tuberculeux, 
518-519. . 

Lecanu, on presence of fibrine in red 
blood-corpuscles, 174. 

Lecithine. See Myeline. 

Lehmann, on Syntonin, 84; on Hemato- 
crystalline, 179. 

Lens, Crystalline, origin of, 65; fibres 
of, epidermoidal cells, 66; reproduc- 
tion of, after extraction for cataract, 
66; see Cataract. ; 

— on the fatty livers of geese, 
370. 

Leucine, in leukemic blood, 205; in 
contents of intestines, 205; in spleen, 
205. 

Leucocytosis, definition of, 201; con- 
founded with pyzemia, 223; physiolo-. 
gical, in digestion, 224; in pregnancy, 
224-225 ; pathological, in scrofulosis, 
226, typhoid-fever, cancer, malignant 
erysipelas, 226; see 526-527. 

Leucorrhea, heterologous nature of se- 
cretion in, 488-489. 

Leukemia, 201-205 ; accompanied either 
by hyperinosis or hypinosis, 201; 
blood in, how distinguished from chy- 
lous blood, 202; fatal tendency of, 
203 ; hemorrhagic diathesis in, 208 ; 
epistaxis, apoplexy, melena in, 208; 
splenic and lymphatic forms, 204; 
difference of morphological elements 
in blood in these two forms, 204; isa 
permanent, progressive leucocytosis, 
205; substances found in blood in, 
205; confounded with pyemia, 223; 


546 
distinction between, and chlorosis, 
261. 

Leydig, on structure of muscle, 80, 83. 

Life, characteristics of, 324 ; duration of 
in different elements, 500-501. 

Lipomata, 3638. i 

Liquefaction, of bone, 464, 496; of in- 
tercellular substance of connective tis- 
sue, 496. 

Liver, hypertrophy and hyperplasy of, 
94; arrangement of capillary vessels 
in acini of, and their relation to hepa- 
tic cells, 102-103; the three constitu- 
ents of capillary network in acini, 103 ; 
secretion of, due to hepatic cells, 159 ; 
its connection with the hemorrhagic 
diathesis, 164; enlargement of, and 
changes in, from infectant matters in 
blood, 246; secondary cancer more 
frequent in, than in lungs, 258, 505; 
increased secretion provoked in, by 
injection of irritating substances into 
blood, 881; fatty physiological and 
pathological, 370-374; intermediate in- 
terchange of matter in, by means of 
biliary ducts, 871-372; three zones of 
change (fat, amyloid matter, pigment), 
in acini of, 871-872; persistence of 
cells, in fatty, 373-374 ; curability of 
fatty condition of, 374; amyloid de- 
generation of, 417-418. 

Lobstein, 93. 

Loculi, of cancer, how produced, 499. 

Locus Niger, 295. 

Long Bones (i.e. osseous tissue of), 
growth in length of, from cartilage, 
in thickness, from periosteum, 451- 
452. 

Ludwig, on molecules of nerves when at 
rest, 328; on salivary glands, 329. 
Lungs, metastases (metastatic deposits) 
in, as a rule due to peripheral throm- 
bosis, 24U, deposition of bone-earth in, 
in mollities ossium, 249; secondary 
cancer less frequent in, than in liver, 
258-505; myeline in, 270; fatty and 
pigmentary degeneration of epithelium 
of air-cells of, 387; gangrene of, from 
gangrenous metamorphosis of throm- 
bus in transverse sinus after caries of 
internal ear, 387; laminated bodies in, 

412. 

Luxuriation, 489. 

Luys, on excretion of starch through 
skin, 420. 

Lymph, conveys corpuscular elements to 

' blood, 191; fibrine of, how it differs 
from fibrine of blood, 192, not perfect 
fibrine, 192. 

Lymph-corpuscles, 209. 

Lymphatic Glands, how distinguished 





INDEX. 


from ordinary secreting glands, 78; 
supply blood with its corpuscular 
elements, 191, 204; affection of, in 
erysipelas and diffuse phlegmonous 
inflammation, 200, in typhoid fever, 
200; leucocytosis due to affection of, 
201; swelling of, in leukemia, 203- 
204; structure of, 206-210; no pass- 
age for pus-corpuscles through, 218; 
deposits in, from tattooing, 218-220; 
deposition of cancerous matter in, 
221, of syphilitic virus in, 221; irrita- 
tion of, in what consists, 222; physio- 
logical irritation of, in digestion, 224, 
in pregnancy, 224-225; affection of, 
in scrofulosis, 226; category of, ex- 
tended, 227; diseases of, from action 
of infectant fluids, 245; amyloid dege- 
neration of (minute arteries and gland- 
cells) 425-427 ; scrofulous changes in, 
439; complete correspondence be- 
tween corpuscles of, and constitutents 
of tubercle, 526. 

Lymphatic Vessels, connection of, with 
phlogistic crasis or hyperinosis, 196 ; 
introduction of pus into, 217. 

Lymphoid Organs, 220-228; diseases of, 
from action of in.ectant fluids, 245. 


Magnetic needle, action of nerves upon, 
325. 

Malignity, not to be confounded with 
heterology, 92, 529. 


‘Malpighi, on fibrine, 167. 


Malpighian Bodies, (spleen) equivalen 
to follicles of lymphatic glands, 224 ; 
amyloid degeneration of, 411, 415. 

(kidney) deposition of silver in, 
247; amyloid degeneration of, and of - 
their afferent arteries, 421-424. 

Marrow, multi-nuclear cells in, 346-347 ; 
a connective tissue, 452; formed from 
osseous tissue, 452; ultimate product 
of development of bone, 452; formed 
from cartilage either directly, 457-459, 
or indirectly (through osseous tissue) 
457; fatty, formation of, 458, normal 
in long bones, 458; in bodies of ver- 
tebre nearly always only small cells 
of, without fat, 458; inflammatory, 
458; very close correspondence be- 
tween, and granulations, 464; forma- 
tion of osteoid tissue and bone from, 
465-466; young (granulations) start- 
ing-point of all heteroplastic develop- 
ment, 470; formation of bone out of, 
in fractures, 483-484; undue forma- 
tion of, in osteomalacia, 489-490 ; very 
close relation of, to pus, 490. 

Marrow-cells, throw out processes (be- 
come jagged) during ossification, 461, 





INDEX. 


466; transformation of, inte bone- 

* corpuscles, 466-467. 

Maturation of Pus, consists in a soften- 
ing of the intercellular substance, 466. 

Meckel, H., on melanzmia, 225, 226; on 
corpora amylacea, 320; on the amy- 
loid substance, 411, 415. 

Meckel, J. F., Junr., on classification of 
neoplasms, 90. 

Medullary Canals of bone. 
sian canals, 

Medullary Cancer, 509. 

—— Fungus. See Medullary Cancer. 
Spaces, primary and secondary, 
473; irregular formation of, in rickets, 
477; excessive formation of, in osteo- 
malacia, 489-490. 

Tissue. See Marrow. 

Meissner, on the two sorts of papille in 
skin, 276; on tactile bodies, 278; on 
nervous plexuses in submucous tissue 
of intestines, 291. 

Melena, in leukemia, 203. 

Melanzmia, 254-258. 

Melanic corpuscles, 170; 259-260; found 
in intermittent fever (slight forms), 
cyanosis, typhoid fever, &c., 260. 

Membrana capsulo-pupillaris, 66. 

Meningitis, Tubercular, 520. 

Mesenterie Glands, swelling of, in ty- 
phoid fever, 201, 226; physiological ir- 
ritation of, producing leucocytosis, 224. 

Metastases (metastatic deposits), 240- 
254 ; in lungs, generally due to throm- 
bosis in peripheral veins, 240; different 
varieties of, dependent upon condition 
of thrombus to which due, 242, ef. 
387; not unfrequently caused by en- 
docarditis on left side of circulation, 
243 ; in kidney, spleen, heart, eye and 
brain, 244; from infectant matters, 
245; from presence of chemical sub- 
stances in blood, in gout, &e., 247- 
248; calcareous, 249-250; from diffu- 
sion of ichorous juices, 250, in cancer, 
258, 505. 

Milk, formation of, 376-878. 

Milza nera, 257. 

Mitral valve, ulceration of, 243; excres- 
censes of, 405. 

Mollities ossium, calcareous deposits in 
lungs and stomach in, 249-250; in 
what it consists, 489-490. 

Morbid Growths. See Pathological Tis- 
sues, 

Morbus Brightii. See Bright’s disease. 

Mucin, 75-76. 

Mucous (Gelatinous, Colloid) Cancer, 526. 

Mucous Membranes, fatty usure of, 381; 
suppuration in, 492-495; development 
of papillary tumours on, 512-513, 


See Haver- 














547 


Mucous Tissue of Umbilical Cord, 74; 
yields mucin on expression, 75; struc- 
ture of, 128-130 ; its close relationship 
to vitreous body, 129. 

Mucous Tubercle, 512. 

Mucous Tumours. See Myxomata, 526, 
531. 

Mucus, fibrils of compared with those of 
fibrine, 168; a product of mucous 
membranes and not present in blood, 
435. 

Mucus-Corpuscles, 49-50; development 
of, on surface of mucous membranes, 
448-449 ; relation of, to pus-corpuscles 
and epithelial cells, 495-496. 

Muller, Heinrich, on radiating fibres of 
retina, 287. 

Muller, Johannes, proposer of name, 
connective tissue, 131; first observer 
of the large, pale nerve-fibres seen in 
spinal cord of Petromyzon fluviatilis, 
309; on correspondence between em- 
bryonic and pathological development, 
442-443 ; on collonema, 526; on cho- 
lesteatoma, 528. 

Mummies, preservation of tissues in, 325. 

Muscle : seldom found in new-formations, 
91; irritability of, 382. 

Striated (red), 79-88; transverse 

and longitudinal strie of, 79; nuclei 

of, ‘79-80; origin of primitive fasciculi 

of, 80; contractility of contents, 81, 

84-85, their structure, 82; progressive 

(fatty) atrophy of, 84; hypertrophy 

of, 938; substitution of, for smooth, 

100; changes produced in ultimate 

elements of, by excitation (irritation), 

328 ; division of nuclei of, from irrita- 

tion, 847-848 ; in embryonic develop- 

ment, 859; softening of, 358-359; 

interstitial so-called fatty degenera- 

tion, or rather fattening of, 363-365 ; 
parenchymatous fatty degeneration of, 
simple, 383-385, inflammatory (second- 
ary) 8938; suppuration in interstitial 

tissue of, 490, 

Smooth (organic, involuntary) 
83-84 ; fascicular arrangement of, 83 ; 
comparison between fibre-cells of, and 
primitive fasciculi of striated muscle, 
83; nuclei of, 89, 83; of skin (arrec- 
tores pilorum), 83; contraction of 
vessels, due to, 85; substitution of 
striped for, 100; of dartos, 138; of 
arteries, 141-142; in ale vespertitio- 
num, 146-147 ; new formation of, in 
fibrous tumours of uterus, 487. 

Myeline, 270-271. 

Myeloid Tumours, 347. 

Myo-carditis, no fibrine set free in, 433, 
cf. 393-394. 








548 


Myo-malacia, 858-359. 
Myxomata, 526-531. 


Nageli, on corpora amylacea, 320. 

Nails, body of, composed of cells, 61, 
65; structure of, 68; growth of, 63 ; 
disease of, 64-65. 

Navel, varieties of, how produced, 126. 

Necrobiosis, definition of, 356; how dis- 
tinguished from necrosis, 358 ; ends in 
softening and disintegration, 358-359. 

Necrosis, distinction between, and necro- 
biosis, 358; of bone, limits of territo- 
ries of bone-cells well shown in, 462-463. 

Neoplasms. See New-Formations. 

Nephritis, parenchymatous and intersti- 
tial, 424, 

Nerve-cells. See Ganglion-cells. 

Nerve-fibres, primitive, their membrane, 
medullary sheath, and axis-cylinder, 
267; white and grey, distinction be- 
tween, 267-268; myeline of, 269-271 ; 
grey atrophy of, 271; axis-cylinder 
(electrical substance) essential consti- 
tuent of, 271; different breadth of; 
272-273; terminations of, 274-292—in 
Pacinian bodies, 274-276—in tactile 
bodies, 276-278—in loops, nowhere 
met with, 284, cf. 274, 278—supposed 
in epithelium-like structures (in mu- 
cous membrane of nose and tongue) 
284-285—in cochlea, 285—in retina, 
285-289—in plexuses (electrical organ 
of silurus, 240, and submucous tissue 
of intestines (human) 291-292; rami- 
fication of, 289-290 ; course and origin 
of, in spinal cord, 305-306. 

Nerve-territories, in skin larger than 
vessel-territories, 281. 

Nerves, seldom found in new-formations, 
92; peripheral, structure of, 265; fas- 
cicular arrangement of, 265 ; intersti- 
tial tissue of, 265, 317-318; grey atro- 
phy of, 271; terminations of, 274-292 ; 
of special sense (olfactory, auditory, 
optic) 284-289; electrical processes 
constantly going on in, 825; changes 
in electrical state of, produced by ex- 
citation (irritation), 328. 

Nervous Centres, 294-320; colour of 
grey matter of, not due to ganglion- 
cells, 294; different kinds of ganglion- 
cells in, 296-300; interstitial substance 
of (neuro-glia) not nervous but a kind 
of connective tissue, 310-311; corpora 
amylacea of, 317-820; made up of an 
infinite number of separate, very mi- 
nute centres, 322-333. 

Nervous Plexuses, in Silurus, 290, 300- 
301; in submucous tissue of intestines, 
291-292. 


| 





INDEX. 


Nervous System, 87, 263-320; its pre- 
tended unity, 266, 322-323; its com+ 
position, 263-264 ; fibrous constituents 
of, 265-294; nervous centres (gunglio- 
nic apparatuses), 294-320. 

Neurilemma, 266; its relation to peri- 
neurium, 318. 

Neuro-glia, 313; 315-316 (see 310-311); 
definition of, 315; a kind of soft con- 
nective tissue with corpuscles, 315- 
316, cf. 313; also found in olfactory 
and auditory nerves, 317-318. 

Neuro-Pathology. See Solidism. 

New Formation, correspondence between 
embryonic and pathological, 442-443 ; 
by means of simple cell-division, 443- 
444; endogenous, of cells, 444-445; 
different kinds of—hyperplastic (direct 
and indirect) and heteroplastic, 446- 
448 ; of vessels, first heteroplastic and 
then hyperplastic, 447. 

New-Formatious. See Pathological Tis- 
sues. 

Nitrate of Silver, results of external and 
internal use of, 247-248, cf. 254. 

Noma, 517. 

Nuclei, constancy of form of. 34; forma- 
tion of (Schleiden’s theory), 35-36 ; 
their importance in maintaining life of 
cells or other elements containing 
them, 37 ; essential to growth of parts, 
38; division of, see Division of nuclei. 

Nucleoli, origin of (according to Schlei- 
den and Schwann), 35; division of, in 
formative irritation, 345. 

Nutrition: its channels, 101-118; con- 
veyance of nutritive juices, 119-139; 
and circulation, 140-165; of liver, 102- 
104; of bone, 115; of teeth, 115; of 
cornea, 116; of semi-lunar cartilages, 
116; of tendons, 120, 123 ; of mucous 
tissue of umbilical cord, 127-130; im- 
portance of capillary membrane in, 
153; no directly regulating influence 
exercised upon, by hyperemia, 156- 
157. 

Nutritive districts, in tendon, 124; see 
Cell-territories. 

Nutritive Irritability, 334-345; often 
tends to death of a part, 334; a pro- 
perty of individual elements of parts, 
not effect of nervous influence, 336. 

Nutritive Irritation, 3834-345; number 
of constituent elements of a part not 
increased in, 384; often cause of death 
of a part, 334; comprises a part of 
what is ordinarily called inflammation, 
335; in kidney, 335-336 ; in cartilage, 
336-3837; in skin, 337; in cornea, 
338, 840-342, 344-345; effects of, not 
due to nervous influence, but to action 





INDEX. 


of individual elements of parts, 336- 
339; often accompanied by formative 
changes, 344. 

Nutritive Restitution (nutritive restitu- 
tional power), 345. 


Olfactory Nerve, its termination in nasal 
mucous membrane, 283-284; neuro- 
glia in, 317-318. 

Optic Nerve, medullary hypertrophy of, 
in retina, 268; termination and con- 
nections of, in retina, 285-287; action 
of light upon, how rendered possible, 
288. 

Osseous Tissue, definition of, 453; me- 
dullary tissue developed out of, 453- 
454; cancer and pus in bone formed 
by direct conversion of, 454; may be 
formed out of marrow and cartilage, 
458; see Bone. 

Ossification, of arteries, real bone formed 
in, 403-404, how distinguished from 
calcification, 407; an inflammatory 
process, 408; of cartilage, 454-456, 
459-461—of marrow, 466-467—of pe- 
riosteum, 467-470, 472. 

Osteoid Tissue, formation of, in cartilage, 
461, in medullary tissue, 466-467, in 
periosteum, 469, 472, 473; definition 
of, 467. 

Osteoma, soft, of the maxille, 472. 

Osteomalacia. See Mollities ossium. 

Osteoporosis, 465. 

Ovary, cerebral matter in, 95; corpora 
Jutea of, 386-387. 


Pacinian (Vaterian) bodies, 274-276. 

Pedarthrocace (scrofulous necrosis of 
the fingers in children) 462. 

Paget, Mr., on myeloid tumours, 347, 

Panniculus adiposus, simple hypertrophy 
of, 94. 

Papille of Skin, network of connective 
tissue corpuscles in, 60-62, 62, 277; 
fine elastic fibres in, 185, 277; nu- 
cleated cells in, 135; nutrition of, 136. 

of bed of nails, 62. 

Papillary portion of skin, 135; nucleated 
cells in, 136. — 

Tumours. See Papillomata, 

Papillomata, 512-516. 

Parasitism of New-Formations, 505-506. 

Parenchyma, definition of term, 339. 

Parenchymatous Exudation, 339-340. 

Inflammation, 436. 

Nephritis, its seat in epithelium 
of cortex of kidney, 424. 

Passive Processes, 356-427; definition 
of, 357; different forms of: necrobio- 
sis (softening), 358-359, induration, 
860, fatty metamorphosis (degenera- 

















549 


tion)—a necrobiotic process—359, 
amyloid degeneration, 409-427. 

Pathological Substitutions, how they dif- 
fer from histological ones, 100. 

Pathological Tissues (New-Formations), 
89-97; definition of, 88; every one 
a physiological prototype, 88; John 
Hunter’s comparison of, 89; vessels 
in, Hunter, Rust, and Kluge’s notions 
respecting, 89; classification of, 91- 
92; rarely contain elements belong- 
ing to more highly organized, and 
especially to muscular and nervous, 
systems, 91-92; chief constituents, 
cells analogous to epithelial cells and 
corpuscles of connective tissues, 91- 
92; not necessarily benignant because 
correspond to physiological tissues, 
97, really reproduction of these tis- 
sues, 97; greater dryness of, less 
power of infection, 252, 530-531; 
nearly all derived from connective 
tissue and its equivalents, 441; mode 
of origin of, a double one (simple cell- 
division, endogenous formation of 
cells), 448-448; really destructive na- 
ture of every kind of, 486; division 
of, into homologous and heterologous, 
486; different duration of life of indi- 
vidual elements of, 500; contagious 
character of, 503-505; parasitism and 
autonomy of, 505-506; nearly all be- 
gin with a proliferation, 507-508; no- 
menclature and classification of, 508- 
510; difference between form and 
nature of, 511; comparison between, 
in animals and vegetables, 582. 

Pearly Tumours, 528-529; only infect 
locally, 530. 

Penis, cauliflower tumours of, 514. 

Perihepatitis, 433. 

Perineurium, 265; compared with neuro- 
glia, 318; its relation to neurilemma, 
S18, 

Periosteum, structure of, 467, 581; de- 
velopment of bone out of, 467-470; 
(see 451-452); conversion of, into car- 
tilage, 469; transformation (patholo- 
gical) of, into osteoid tissue and bone, 
472; formation of bone out of, in 
fractures, 483. 

Periostitis, 467-468. 

Peripolar state of nerves, 328. 

Peristaltic Movements of intestines, 292. 

Petrifaction of Arteries, 407. 

Petromyzon fluviatilis (lamprey), spin: 
cord of, its structure, 308-310, no me- 
dullary matter in, only simple, pale, 
nerve-fibres, 310. 

Peyer’s patches, really lymphatic glands, 
226-227, 


550 


Phlebitis, supposed formation of pus in 
veins in, 230-231; substitution of term 
thrombosis for, 233; an inflammation 
affecting walls and not contents, of a 
vessel, 236; no necessary coagulation 
of blood in vessel at part affected, 236. 

Phlogistic Crasis. See Crasis. 

Phyma, 510. 

Physalides (brood-cavities) 444-445, 

Physaliphores (cells containing vesicles) 
444. 

Physiological Types, all pathological tis- 
sues (neoplasms, new-formations) to 
be referred to, 88. Cf. 582-533. 

Pigment, in eclls of choroid membrane, 
39; in mucus-corpuscles, 49-50; seat 
of, in acini of, liver (pigment-zone) 
872; in pulmonary epithelium, 387. 

Pigment-cells, produced by transforma- 
tion of epidermic cells, 66-67 ; in blood 
in ague, and melanemia, 256-257 ; 
distinction between, and fat-granule 
cells, 887-888 ; in catarrhal pneumo- 
nia, 387. 

Piorry, his crusta granulosa (Hemitis) 
187, 228. 

Plants, growth of, 45-47; 
532-533. 

Plaques Muqueuses, 282, 512. 

‘Pleurisy, fibrine produced in exudation 
of, 192-193; buffy coat in, 193-194; 
inspissation of pus in, 214; metastatic, 
due to ichorrhemia, 249-250. 

Plexuses, nervous, in Silurus, 291, 301; 
in submucous tissue of intestines, 291- 
292. 

Pneumogastric Nerve, effects of section 
of, explained, 351-352. 

Pneumonia, buffy coat in, 193-194; in- 
crease of colourless corpuscles in, when 
accompanied by swelling of bronchial 
glands, 228; how caused by section 
of pneumogastric, 352; catarrhal, for- 
mation of pigment in, 387, 

Polli, on slowly coagulating (brady-) 
fibrine, 198, 194. 

Polysarcia, how produced, 94, 363. 

Portal, on central canal of spinal cord, 
303. 

Potash, provocative of ciliary movement, 
231. 

Pregnancy, enlargement of vessels in, 
146; leucocytosis in, 224-225 ; hyperi- 
nosis in, accounted for, 225. 

Prostate, concretions of. See Prostatic 
concretions. 

Prostatic Concretions (laminated amy- 
loid bodies) of, 411-413; appearance 
and size of, 412; reactions of, with 
iodine, 413. 

Puerperal fever, so called pyemia in, 


tumours of, 





INDEX. 


223-225; embolical aivtastases in lungs 
in, 240, 

Pulmonary Artery, embolia of, 240-241. 

Purkinje, on lining membrane of cere- 
bral ventricles, 311-812; on corpora 
amylacea, 320; on ciliary movement, 
Sol. 

Purpura, 163-164. 

Pus, corpuscles of, see Pus-Corpuscles ; 
compared with cancer juice, 91; for- 
merly thought to be secretion from 
blood, 212; physiological reabsorp- 
tion of, 212; is never reabsorbed as 
pus, 213; fluid part of, reabsorbed, 
213; inspissation (cheesy metamor- 
phosis) of, 213, 215; serum of, 218- 
214; fatty metamorphosis of corpus- 
cles of, 216 ; reabsorption of, in shape 
of emulsion (pathological milk) 216; 

_ intravasation of, into veins and lym- 
phatic vessels, 217; not present in 
softening thrombi, 334; in bone, 
formed by direct transition out 
of osseous tissue, 453-454; maturation 
of, 466; very close relation of, to 
medullary tissue, 490, and granula- 
tions, 466, 497 ; formation of, out of 
epithelium (skin, 491-492, mucous 
membranes, 482-493), 490-494—out 
of connective tissue, 490, 495-496; 
no solvent power, 491-497; corre- 
spondence of first stage of, to that of 
cancer, cancroid and sarcoma, 499 ; 
relation of, to tubercular infiltration, 
519 (ef. 215) ; resemblance of' its cells 
and nuclei to those of tubercle, 521; 
hematoid nature of, 527. 

Pus-Corpuscles, 49-50; great resemblance 
between, and colourless blood-corpus- 
cles, 182, 212, how they can be distin- 
guished, 188, 527; structure of, 218; 
shrivelling of, 214; fatty degeneration 
of, 216; cannot pass through lympha- 
tic glands, 218; when not furnished 
by an ulcerating surface, derived from 
epithelial cells, 449; development of, 
from epithelial cells, 491-493; relation 
of, to mucus- and epithelial cells, 493- 
494; development of, from connec- 
tive tissue corpuscles, 490, 495-496. 

Pustules, formation of, 491-492; vario- 
lous, 492. 

Putrilage, definition of, 500. 

Pyemia, 211-251; definition of, 211; 
confounded with leucocytosis and leu- 
keemia, 2233; no pus-corpuscles in 
blood in, excepting when an abscess 
has emptied itself into a vein, 228- 
229; latent, 244; if retained, to be 
used as a collective name for seve- 
ral dissimilar processes (leucocytosis, 


INDEX. 


thrombosis, ichorrhemia) 250. See 
Phlebitis, Thrombosis, Leukemia, 
Leucocytosis, Ichorrhzmia. 


Rabbits, rhythmical movements in arte- 
ries of ears of, 148. 

Recurrence, local, of tumours, after ex- 
tirpation, 503. 

Redfern, Dr., his experiments on cartil- 
age, 336. 

Reichert, on the fibres of connective tis- 
sue, 70; his theory of the formation 
of connective tissue, 71-72. 138, 169; 
on the continuity of tissues, 97-98 ; 
discoverer of Hemato-crystalline, 179- 
180; on the connective-tissue frame- 
work of the body, 441-442. 

Reinhardt, on origin from pus of. much 
of what is called tubercle, 215 (ef. 
519); on fat-granule masses, 377; on 
tuberculosis and tuberculous matter, 
519. 

Remak, on germinal membrane in con- 
nection with formation of glands, 66 ; 
on division of blood-corpuscles in em- 
bryo, 190 ; his mistake with regard to 
brain-sand, 416; on cleavage of yolk, 
442. 

Respiratory Substance of red blood cor- 
puscles, 262-263 ; paralysis of, in ty- 
phoid fevers, 262, from the action of 
different chemical substances, 262. 

Rete Malpighii (mucosum) 57, 60, 61, 
62, &e. 

Retina, medullary hypertrophy of optic 
nerve in, 268; structure of, 285-289 ; 
its sensibility to light, what due to, 
288 ; blind spot in, 288; bodies akin 
to corpora amylacea found in, 320, 

Rhachitis. See Rickets. 

Rickets, development of bone, best ob- 
served in, 461; different processes of 
growth of bone, as seen in, 476-481 ; 
in what it consists, 476; irregularity 
of calcification in, 476; infractions 
and inflexions of bones in, 478 ; irre- 
gular formation of medullary spaces 
in, 477. 

Ricord, on seat of virus in-bubo, 221-512, 

Robin, on perineurium, 265; his plaques 
a plusieurs noyaux in marrow of bones, 
348 ; on tubercular meningitis, 520. 

Rokitansky, on atheroma, 402. 

Rollet, on structure of muscle, 80. 
Rouget, his explanation of supposed ex- 
cretion of starch through skin, 420. 
Rust, on independent vascular system of 
new-formations, 89; 200. 
Ruysch, on blood-vessels, 108. 


Salt, production of cataract in frogs by 





551 


injection of, 154; its action upon red 
blood-corpuscles, 173. 

Salter, Dr. Hyde, on connection between 
tendon and muscle, 99. 

Sarcoma, mammary, 90; pancreatic, 90, 
correspondence between first stage of * 
and that of pus, 499; in France called 
fibro-plastic tumour, 509 ; cheesy me- 
tamorphosis of, 524; definition of, 582: 
not unfrequently malignant, 582. 

Scherer, on correspondence between sub- 
stances found in leukemic blood, and 
in spleen, 205. 

Schiff, on rhythmical movements of arte- 
ries, 148. 

Schleiden, 30; on development of nu- 
cleoli, nuclei and cells, out of free 
blastema, 35-36, 449. 

Schmidt, Carl, his analyses of amyloid 
spleens, 415. 

Schultz, Carl Heinrich, on effects of ad- 
dition of aqueous solution of iodine to 
blood-corpuscles, 173; on melanic 
blood-corpuscles, 260 ; on necrobiosis, 
358. 

Schultze, Max., on termination of nerves 
of nasal mucous membrane, 285. 

Schwann, 29; 80; 35; on intercellular 
substance of tissues, 41; his theory 
of the formation of connective tissue, 
70-71 ; on embryonic and pathological 
development, 442; 509. 

Sclerema, definition of, 526. 

Sclerosis, of arteries, 403 ; definition of, 
468; of intercellular substance of pe- 
riosteum, 469. 

Scrofulosis, leucocytosis in, 226 ; changes 
in lymphatic glands in, 489, 

Scrotum, ruge of, 187, 

Scurvy, 163-164. 

Sebaceous Cysts. See Epidermic Cysts. 

Glands, 374-375. 

Matter, compared with colos« 
trum, 376. 

Secreting organs, specific affinities of, 
157-159, 332. 

Secretion, definition of, 492-493. 

Secretory (Exudative) Inflammation, 436. 

Section of nerves, effects of, explained 
and analyzed, 351-352; cf. 150, 156, 
382. 

Semi-lunar Cartilages, nutrition of, 117. 
118; not cartilage at all, but tendon, 
119. 

Septhemia. See Ichorrhemia, 

Siegmund, G., on presence of creatine in 
muscular fibres of uterus, 84. 

Silicie acid, 170. 

Silurus (malapterurus), plexiform ar 
rangement of nerve-fibres in electrical 
organ of, 290, 300. 








552 


Silver, salts of, deposition of, in skin and 
kidneys, 274, cf. 254. 

Skin, papille of, see Papille; effect of 
direct irritation of, not limited to par- 
ticular nerve-territories, 8338 ; see Co- 
rium and Cuticle. 

Sluggish layer in capillaries, 185. 

Small Pox, effects of, upon nails, 65; 
contagion of, 254; pustules of, 492. 
Snellen, on section of fifth pair of nerves, 

352. : 

Soda, provocative of ciliary movement, 
331. 

Softening (malacia) a form of (passive) 
degeneration, 358. 

Solidism (Neuro-pathology), 44; 264; 
288; 291; 298; 322-824; 3386-339; 
849-350; 504; 583. 

Specific affinities, 157-159, 382. 

Spinal Cord, three kinds of ganglion- 
cells in grey matter of, motor, sensi- 
tive and sympathetic, 296-300; white 
and grey matter of, 302-303; central 
canal of, 308-804 ; distribution of the 
three kinds of ganglion-cells in, 305 ; 
lobular arrangement of fibrous consti- 
tuents of, 805-306; commissures of, 
306; of petromyzon (lamprey), 308- 
809 ; central thread of ependyma of, 
304, 315; grey (gelatinous) atrophy 
of, 319. ; 

Spleen, its connection with the hemor- 
rhagic diathesis, 164; swelling of, in 
typhoid fever, 200; in leukemia, 203; 
intimately concerned in development 
of blood, 204; increased action of, in 
leukemia, 205; colourless corpuscles 
conveyed away from, by lymphatics, 
not by veins, 209; a lymphoid organ, 
its Malpighian bodies being equivalent 
to follicles of a lymphatic gland, 227- 
228; minute metastatic deposits in, 


243-244 ; tumefaction of, presence of : 


noxious matters in blood, 246; con- 
nection between its diseases and those 
of liver and kidney, 246; enlargement 
of, in ague and melanemia, 256-257 ; 
occurrence of pigment-cells in blood 
generally due to affection of, 258 ; 
myeline in, 271; amyloid degenera- 
tion of (sagoey spleen) 411; analyses 
of amyloid spleens, 415, 

Spondylarthrocace (caries of vertebra), 
inspissation of pus in, 215-216, 

Stannius, on pale nerve-fibres met with 
in spinal marrow of Petromyzon flu- 
viatilis, 310. 

Starch, in vegetable cells, 45-46 ; sup- 
posed excretion of through skin ae- 
counted for, 420, 

Steatoma, 508-509. 





INDEX, 


Stellule Verheynii, 389. 

Stiebel, on pigment-cells in blood (mee 
laneemia), 256. 

Stilling, on central canal of spinal cord, 
303. ; 

Stimuli, specific relations or affinities of, 
332; irritating of inflammatory (irri- 
taments) necessary for production of 
inflammation, 429. . 

Stomach, arrangement of capillaries in 
muscular coat of, 80; deposits of bone- 
earth in mucous membrane of, in 
mollities ossium, 249; fatty usure of 
mucous membrane of, 381; inflamma- 
tions of, 433. 

Subcutaneous tissue, diffuse gangrenous 
inflammation of, from ichorrhenia, 
250. 

Substantia nigra, 295. 

fusca, 295. 

Substitution of Tissues, histological, 99- 
100; pathological, 100; in bone, 452, 
470. 





Sugar, its action upon red blood-corpus- 
cles, 172. 

Sulphuric Acid, action of, on cellulose 
(after application of iodine and alone), 
3l—on corpora amylacea of brain 
with iodine), 820—on cholestearine 
(with iodine and alone), 400. 

Supiot, Mme., 249. 

Suppuration, in bone, 465; a pure pro- 
cess of luxuriation, 489; two forms 
of, superficial, in epithelium, 490, 
aud deep, in connective tissue, 49u, 
495-496; ulcerative, 497; eroding 
form of, 500. 

Sympathetic Nerve, effects of section of, 
150, 156; ganglion-cells of, in spinal 
cord (of man), 297-300, 305, (of pe- 
tromyzon fluviatilis) 308-309, deposi 
tion of pigment in, 295-296. 

Syntonin, found in striated and non- 
striated muscle, 84. 


Tabes dorsalis, 319. 

Tactile bodies, 276-278, 288, 288. 

Tattooing, deposits caused by, in lym- 
phatic glands, 218-220. 

Teeth, nutrition of, 115. 

Teichmann, on Hemine, 178. 

Tendo Achillis, 119-123. 

Tendons, connection of, with muscles, 
99; structure of, 120-122; growth of, 
123; nutrition of, 124 ; nutritive dis- 
tricts of, 124. 

Textor, 346. 

Thrombi, puriform softening of, 2383, 
287 5; colourless corpuscles found in, 
not pus-, but blood-corpuscles, 334- 
885; speedy disappearance of red 


INDEX. 


blood-corpuscles from, 235; detach- 
ment of fragments from softening, 
238, 406; prolonged, and their im- 
port, 239; autochthonous, 239; con- 
dition of, important in determining 
character of metastatic deposits arising 
from, 241, cf. 387. 

Thrombosis, 232-238; may arise from 
phlebitis, arteritis, endocarditis, 236 ; 
of transverse sinus, from caries of in- 
ternal ear, 387. 

Thymus Gland, essentially a lymphatic 
gland, 227; endogenous cell-formation 
in, 444-445. 

Tigri, on melaneemia, 257. 


_ Tissues, classification of normal, 55-56, 


of pathological, 91-92, 509-510. 

Tongue, follicles of root of, equivalent to 
follicles of lymphatic glands, 227 ; ter- 
minations of nerves in mucous mem- 
brane of, 285. 

Tonsils, really lymphatic glands, 22’. 

Traer, Mr. James, on contraction of ale 
vespertilionum, 147. 

Traube, on section of pneumogastric 
nerve, 332. 

Trigeminus (fifth pair of nerves) effects 
of section of, explained, 351-352. 

Tuber, definition of, 502. 

Tubercle, neglected as being a crude pro- 
duct, 90; cheesy products regarded as, 
in great measure really derived from 
pus, 215, cf. 520; phyma, as a new 
name for, 510; as a designation for an 
external form, 517; infiltration and 
granulation of, 517; corpuscles of, 
518; real, only exist in a knotted or 

granular form, 619-520; its origin 
from connective tissue, 520-521; nu- 
clei and cells of, how they resemble 
those of pus and differ from those of 
cancer, 522; fatty degeneration (cheesy 
metamorphosis) of, 522; solitary, of 
brain, 522-523 ; obliteration of vessels 
of, 523-524; lymphoid nature of, 527. 

Tubercle, mucous, 512. 

Tubercle-corpuscles, 518. 

Tubercular Infiltration of lungs, due to 
presence within alveoli of shrivelled-up 
pus-cells, 215, 518; inflammatory ori- 
gin and non-tuberculous nature of, 519. 

Tubercular Meningitis, 520. 

Tuberculization, of Pus, 215. 

Tumeur perlée, 528. 

Tumours: see the specific names; tu- 
berous and infiltrated, 471; compound 
nature of tuberous, and mode of their 
enlargement, 501-502; local recur- 
rence of, after extirpation, its cause, 
503 ; vegetable, 533. 

Typhoid-fever, hypinosis in, 200; in- 





553 


crease of colourless corpuscles in, 200; 
swelling of mesenteric glands and 
spleen in, 201, cf. 226; melanic_cor- 
puscles in blood in, 260; deposition 
of pigment in ganglia of sympathetic 
in, 295. See 439. 

Typhoid fevers, diminution of respiratory 
power of red blood-corpuscles in, 262. 

Typhous matter, not an exudation, 440. 

Tyrosine, on liver, 205; in contents of 
intestines, 205 ; in spleen, 205. 


Ulcer, atheromatous, 382; description 
of, 404. 

Ulceration, 497 ; sanious, 500. 

Umbilical Cord, 125-180; really non- 
vascular, 125; capillaries of, 126 ;. per- 
sistent portion of, its limits, how de- 
termined, 127; deciduous portion of, 
127; mucous tissue of, 128-130; nu- 
trition of, 128-130; structure of, 128- 
129. 





Vessels, their relation to umbili- 
eal cord, 126; great thickness of mus- 
cular coat of, 127. 

Urate of Soda, in gout, 248; deposition 
of, in kidney, 248. 

Urea, diminution of secretion of, in amy- 
loid degeneration of kidney, 423-424. 

Uric acid, in leukemic blood, 205; in 
spleen, 205. 

Uterus, creatine in muscular fibres of, 
84; ciliated epithelium of mucous 
membrane of, replaced by squamous, 
epithelium in pregnancy, 100; new 
formation of muscular fibres, in fibrous 
tumours of, 487; cauliflower turiours 
of neck of, 514-516. 

Utricle, primordial, 31; 45-46. 


Vagina, substitution, in prolapsed, of 
epidermis for epithelium, 100. 

Vagus (pneumogastric nerve) effects of 
section of, explained, 351-352. 

Valentin, on lining membrane of cere- 
bral ventricles, 311; on ciliary move- 
ment, 331. 

Varicose veins, how produced, 153. 

Vasa Serosa, substitute for, 75, 114. 

Vascular canals of bone. See Haversian 
or Medullary canals. 

System, everywhere closed by 

membranes, 144. 
— territories. 

ries. 








See Vessel-territo- 





theory (of inflammation) 428. 

Vascularity, import of, 87-88. 

Vegetable Tumours, 532-533. 

Veins, longitudinal muscular layers in, 
86; muscular tissue in superficial cu- 
taneous, 142; small, formation and 


504 


course of, 144-145; middle coat of, 
144-145 ; epithelium of, 145; smallest, 
entirely composed of connective tissue 
and epithelium, 146 ; rhythmical move- 
ments of, in wings of bats, 148; ac- 
tivity of, chiefly and sometimes wholly 
due to their elastic tissue, 152; vari- 
cose, how produced, 153 ; introduction 
of pus into, 217. 

Verjauchung, definition of, 500. 

Vertebre, caries of. See Spondylar- 
throcace. 

Vesalius, 28, 339. 

Vessels, development of, in new-forma- 
tions, 89, cf. 447; action of, in what 
really consists, 101-102; transudation 
from, how perhaps favoured and how 
impeded, 102; of liver, 102-104; of 
brain, 104-105; of muscular coat of 
stomach, 105-106 ; in cartilage of new- 
born child, 107; of bone, 108-112; 
not all subject to special nervous in- 
fluence, 283; new formation of, 447 
(note). 

Vessel-Territories (districts of tissue be- 
longing to vessels), 114; 146; 156; 
281-282. 

Vienna School, on pyxemia, 223; on 
amyloid degeneration, 409, 410; on 
inflammation, 428-429; on typhous 
matter, 440; on tubercle, 519. 

Villi, Intestinal, 365-869; structure of, 





INDEX. 


866; absorption of fat by, 367-568: 
muscular fibres and contractility of. 
367-368 ; retention of fat in, 368-369: 
amyloid degeneration in, 422. 
Villous Tumours. See Papillomata. 
Vital Activity, irritation essential to pro- 
duction of, 325; general forms of 
(function, nutrition, formation), 326. 
Vitreous body, its relationship to jelly 
of Wharton (mucous tissue) 129. 
Vogt, C., on fibres of lens, 66. 


Wagner, Rud., on the two sorts of pa- 
pille in skin, 276; on tactile bodies, 
277; on ramification of nerve-fibres, 
290. 

Waxy Degeneration. 
generation. 

Weber, E. H., on colourless blood-cor- 
puscles, 184, 185. 

Wharton, so-called jelly of, 126, 129. 

Willis, Thomas, on submucous layer of 
intestines, 292, — 

Woorara, effects of, in paralyzing nerves, 
338. 


See Amyloid De- 


Yolk, cleavage of, 442. 


Zimmermann, on relation between pus , 
and colourless blood-corpuscles, 188, 
527; on development of red blood 
corpuscles, 259. 





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